RS-ADR: A Reference Standard for Adverse Drug Reaction Signal Assessment by Integrating Real-World Evidence and Controlled Vocabularies (Preprint)

2021 ◽  
Author(s):  
Suehyun Lee ◽  
Jeong Hoon Lee ◽  
Grace Juyun Kim ◽  
Jong-Yeup Kim ◽  
Hyunah Shin ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Real World ◽  
Adverse Event Reporting System ◽  
Hepatic Function ◽  
Adverse Event Reporting ◽  
Reference Standard ◽  
Real World Data ◽  
Controlled Vocabularies ◽  
Real World Evidence

BACKGROUND Pharmacovigilance using real-world data (RWD), such as multicenter electronic health records (EHRs), yields massively parallel adverse drug reaction (ADR) signals. However, proper validation of computationally detected ADR signals is not possible due to the lack of a reference standard for positive and negative associations. OBJECTIVE To develop a reference standard for ADR (RS-ADR) to streamline the systematic detection, assessment, and understanding of almost all drug-ADR associations suggested by RWD analyses. METHODS We integrated well-known reference sets for drug-ADR pairs, including Side Effect Resource (SIDER), Observational Medical Outcomes Partnership, and EU-ADR. We created a pharmacovigilance dictionary using controlled vocabularies and systematically annotated EHR data. Drug-ADR associations computed from MetaLAB and MetaNurse analyses of multicenter EHRs and extracted from the FDA Adverse Event Reporting System (FAERS) were integrated as ‘empirically determined’ positive and negative reference sets by means of cross-validation between institutions. RESULTS The RS-ADR consisted of 1,344 drugs, 4,485 ADRs, and 6,027,840 drug-ADR pairs with positive and negative consensus votes as pharmacovigilance reference sets. After curation of the initial version of RS-ADR, novel ADR signals such as ‘famotidine’-‘hepatic function abnormal’ were detected and reasonably validated by RS-ADR. While the validation of the entire reference standard is challenging, especially with this initial version, the reference standard will improve as more RWD participate in the consensus voting with advanced pharmacovigilance dictionaries and analytic algorithms. One can check if a drug-ADR pair has been reported by our web-based search interface for RS-ADRs available at https://bioemr2.snubi.org:19108/. CONCLUSIONS RS-ADRs enriched with the pharmacovigilance dictionary, ADR knowledge, and real-world evidence from EHRs may streamline the systematic detection, evaluation, and causality assessment of computationally detected ADR signals.

scholarly journals Age and Gender Disparities in Adverse Events Following COVID-19 Vaccination: Real-World Evidence Based on Big Data for Risk Management

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaomo Xiong ◽  
Jing Yuan ◽  
Minghui Li ◽  
Bin Jiang ◽  
Z. Kevin Lu
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Gender Disparities ◽  
Permanent Disability ◽  
Younger Adults ◽  
Age And Gender ◽  
Real World Evidence ◽  
And Gender

Background: Two coronavirus disease 2019 (COVID-19) vaccines have received emergency use authorizations in the U.S. However, the safety of these vaccines in the real-world remains unknown.Methods: We reviewed adverse events (AEs) following COVID-19 vaccination among adults in the Vaccine Adverse Event Reporting System (VAERS) from December 14, 2020, through January 22, 2021. We compared the top 10 AEs, serious AEs, along with office and emergency room (ER) visits by age (18–64 years, ≥65 years) and gender (female, male).Results: There were age and gender disparities among adults with AEs following COVID-19 vaccination. Compared to younger adults aged between 18 and 64 years, older adults were more likely to report serious AEs, death, permanent disability, and hospitalization. Males were more likely to report serious AEs, death, and hospitalization compared to females.Conclusions: COVID-19 vaccines are generally safe but possible age and gender disparities in reported AEs may exist.

Multiple sclerosis as an adverse drug reaction: clues from the FDA Adverse Event Reporting System

2018 ◽  
Vol 17 (9) ◽  
pp. 869-874 ◽  
Author(s):  
Ippazio Cosimo Antonazzo ◽  
Emanuel Raschi ◽  
Emanuele Forcesi ◽  
Trond Riise ◽  
Kjetil Bjornevik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Drug Reaction ◽  
Adverse Event ◽  
Drug Reaction ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Event Reporting

scholarly journals Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States

2021 ◽  
Vol 8 ◽  
Author(s):  
Yinghong Zhai ◽  
Xiaofei Ye ◽  
Fangyuan Hu ◽  
Jinfang Xu ◽  
Xiaojing Guo ◽  
...  
Keyword(s):  
Cardiac Failure ◽  
Real World ◽  
Cardiovascular Events ◽  
Adverse Event Reporting System ◽  
Torsade De Pointes ◽  
Onset Time ◽  
The United States ◽  
Cardiovascular Complications ◽  
Adverse Event Reporting ◽  
Real World Evidence

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1–Q3: 4–85 days) for ischemic heart disease, with the longest time being 68 days (Q1–Q3: 21–139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

scholarly journals Adverse outcomes associated with the treatment of Toxoplasma infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ahmed M. Shammaa ◽  
Thomas G. Powell ◽  
Imaan Benmerzouga
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Real World ◽  
Odds Ratio ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Adverse Outcomes ◽  
Reporting Odds Ratio ◽  
Real World Data ◽  
Suspect Drug

AbstractAdverse outcomes associated with the treatment of Toxoplasma gondii infections in patients with various health backgrounds have not been characterized. The aim of this study was to identify the adverse outcomes and adverse events associated with the current clinical treatments of Toxoplama gondii infections using real world data reported to the FDA adverse event reporting system (FAERS). Data submitted to FAERS between 2013 and 2019 was retrieved and analyzed. Reporting odds ratio of death was calculated for the drugs having ≥ 25 reports of adverse outcomes. The adverse event profiles for the same drugs were analyzed and the reporting odds ratio was calculated relative to all other drugs used in the treatment of Toxoplasma infections. There were 503 cases reporting the treatment of Toxoplasma infections in the FAERS database. Death (DE) was the adverse outcome in 102 reports, of which 23 (22.5%) anti-Toxoplasma drugs were listed as the primary suspect drug (PS). Clindamycin (2.04; 1.07–3.90) followed by pyrimethamine (1.53; 0.99–2.36) were the most likely to be associated with death. Adverse events analysis suggest that sulfonamides formulations may have a less favorable safety profile. Our study represents the first real-world analysis of adverse outcomes and events associated with the treatment of Toxoplasma infections. Our findings support the need to better understand the current first-line agents for Toxoplasma infections, in addition to underscoring the need to identify safer regimens.

scholarly journals Real-world evidence: perspectives on challenges, value, and alignment of regulatory and national health technology assessment data collection requirements

2021 ◽  
Vol 37 ◽  
Author(s):  
Hannah Sievers ◽  
Angelika Joos ◽  
Mickaël Hiligsmann
Keyword(s):  
Health Technology Assessment ◽  
Technology Assessment ◽  
Real World ◽  
Health Technology ◽  
Practical Experience ◽  
Added Value ◽  
Real World Data ◽  
Conflicting Demands ◽  
Real World Evidence ◽  
Semistructured Interviews

Abstract Objective This study aims to assess stakeholder perceptions on the challenges and value of real-world evidence (RWE) post approval, the differences in regulatory and health technology assessment (HTA) real-world data (RWD) collection requirements under the German regulation for more safety in drug supply (GSAV), and future alignment opportunities to create a complementary framework for postapproval RWE requirements. Methods Eleven semistructured interviews were conducted purposively with pharmaceutical industry experts, regulatory authorities, health technology assessment bodies (HTAbs), and academia. The interview questions focused on the role of RWE post approval, the added value and challenges of RWE, the most important requirements for RWD collection, experience with registries as a source of RWD, perceptions on the GSAV law, RWE requirements in other countries, and the differences between regulatory and HTA requirements and alignment opportunities. The interviews were recorded, transcribed, and translated for coding in Nvivo to summarize the findings. Results All experts agree that RWE could close evidence gaps by showing the actual value of medicines in patients under real-world conditions. However, experts acknowledged certain challenges such as: (i) heterogeneous perspectives and differences in outcome measures for RWE generation and (ii) missing practical experience with RWD collected through mandatory registries within the German benefit assessment due to an unclear implementation of the GSAV. Conclusions This study revealed that all stakeholder groups recognize the added value of RWE but experience conflicting demands for RWD collection. Harmonizing requirements can be achieved through common postlicensing evidence generation (PLEG) plans and joint scientific advice to address uncertainties regarding evidence needs and to optimize drug development.

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