A Computational Framework for Identifying Age Risks in Drug-Adverse Event Pairs

The identification of associations between drugs and adverse drug events (ADEs) is crucial for drug safety surveillance. An increasing number of studies have revealed that children and seniors are susceptible to ADEs at the population level. However, the comprehensive explorations of age risks in drug-ADE pairs are still limited. The FDA Adverse Event Reporting System (FAERS) provides individual case reports, which can be used for quantifying different age risks. In this study, we developed a statistical computational framework to detect age group of patients who are susceptible to some ADEs after taking specific drugs. We adopted different Chi-squared tests and conducted disproportionality analysis to detect drug-ADE pairs with age differences. We analyzed 4,580,113 drug-ADE pairs in FAERS (2004 to 2018Q3) and identified 2,523 pairs with the highest age risk. Furthermore, we conducted a case study on statin-induced ADE in children and youth. The code and results are available at https://github.com/Zhizhen-Zhao/Age-Risk-Identification

Data Sources for Drug Utilization Research in Brazil—DUR-BRA Study

Background: In Brazil, studies that map electronic healthcare databases in order to assess their suitability for use in pharmacoepidemiologic research are lacking. We aimed to identify, catalogue, and characterize Brazilian data sources for Drug Utilization Research (DUR).Methods: The present study is part of the project entitled, “Publicly Available Data Sources for Drug Utilization Research in Latin American (LatAm) Countries.” A network of Brazilian health experts was assembled to map secondary administrative data from healthcare organizations that might provide information related to medication use. A multi-phase approach including internet search of institutional government websites, traditional bibliographic databases, and experts’ input was used for mapping the data sources. The reviewers searched, screened and selected the data sources independently; disagreements were resolved by consensus. Data sources were grouped into the following categories: 1) automated databases; 2) Electronic Medical Records (EMR); 3) national surveys or datasets; 4) adverse event reporting systems; and 5) others. Each data source was characterized by accessibility, geographic granularity, setting, type of data (aggregate or individual-level), and years of coverage. We also searched for publications related to each data source.Results: A total of 62 data sources were identified and screened; 38 met the eligibility criteria for inclusion and were fully characterized. We grouped 23 (60%) as automated databases, four (11%) as adverse event reporting systems, four (11%) as EMRs, three (8%) as national surveys or datasets, and four (11%) as other types. Eighteen (47%) were classified as publicly and conveniently accessible online; providing information at national level. Most of them offered more than 5 years of comprehensive data coverage, and presented data at both the individual and aggregated levels. No information about population coverage was found. Drug coding is not uniform; each data source has its own coding system, depending on the purpose of the data. At least one scientific publication was found for each publicly available data source.Conclusions: There are several types of data sources for DUR in Brazil, but a uniform system for drug classification and data quality evaluation does not exist. The extent of population covered by year is unknown. Our comprehensive and structured inventory reveals a need for full characterization of these data sources.

Evaluation of adverse effects/events of genetically modified food consumption: a systematic review of animal and human studies

Objective A systematic review of animal and human studies was conducted on genetically modified (GM) food consumption to assess its safety in terms of adverse effects/events to inform public concerns and future research. Methods Seven electronic databases were searched from January 1st 1983 till July 11th 2020 for in vivo, animal and human studies on the incidence of adverse effects/events of GM products consumption. Two authors independently identified eligible studies, assessed the study quality, and extracted data on the name of the periodical, author and affiliation, literature type, the theme of the study, publication year, funding, sample size, target population characteristics, type of the intervention/exposure, outcomes and outcome measures, and details of adverse effects/events. We used the Chi-square test to compare the adverse event reporting rates in articles funded by industry funding, government funding or unfunded articles. Results One crossover trial in humans and 203 animal studies from 179 articles met the inclusion criteria. The study quality was all assessed as being unclear or having a high risk of bias. Minor illnesses were reported in the human trial. Among the 204 studies, 59.46% of adverse events (22 of 37) were serious adverse events from 16 animal studies (7.84%). No significant differences were found in the adverse event reporting rates either between industry and government funding (χ2 = 2.286, P = 0.131), industry and non-industry funding (χ2 = 1.761, P = 0.185) or funded and non-funded articles (χ2 = 0.491, P = 0.483). We finally identified 21 GM food-related adverse events involving 7 GM events (NK603 × MON810 maize, GTS 40-3-2 soybean, NK603 maize, MON863 maize, MON810 maize, MON863 × MON810 × NK603 maize and GM Shanyou 63 rice), which had all been on regulatory approval in some countries/regions. Conclusion Serious adverse events of GM consumption include mortality, tumour or cancer, significant low fertility, decreased learning and reaction abilities, and some organ abnormalities. Further clinical trials and long-term cohort studies in human populations, especially on GM food-related adverse events and the corresponding GM events, are still warranted. It suggests the necessity of labelling GM food so that consumers can make their own choice.

Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1.Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.