Adverse events associated with potential drugs for COVID-19: a case study from real-world data
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ABSTRACT:
SUBMITTER: Jing Y
PROVIDER: S-EPMC7543289 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Project description:A COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) has recently been authorized for adolescents in the US. However, the impact of adverse events on adolescents after vaccination has not been fully investigated. To assess the safety of the COVID-19 vaccine in adolescents, the incidence of adverse events (AEs) in adolescents and adults was compared after vaccination. We included 6304 adolescents (68.14 per 100,000 people) who reported adverse events using vaccine adverse event reporting system (VAERS) data from 10 May 2021 to 30 September 2021. The mean age was 13.6 ± 1.1 years and women (52.7%) outnumbered men. We analyzed severe and common adverse events in response to the COVID-19 vaccine among 6304 adolescents (68.14 per 100,000 people; 52% female; mean age, 13.6 ± 1.1 years). The risk of myocarditis or pericarditis among adolescents was significantly higher in men than in women (OR = 6.61, 95% CI = 4.43 to 9.88; p < 0.001), with a higher frequency after the second dose of the vaccine (OR = 8.52, 95% CI = 5.79 to 12.54; p < 0.001). In addition, severe adverse events such as multisystem inflammatory syndromes, where the incidence rate per 100,000 people was 0.11 (n = 10), and the relative risk was 244.3 (95% CI = 31.27 to 1908.38; p < 0.001), were significantly higher in adolescents than in adults. The risk of the inflammatory response to the COVID-19 vaccine, including myocarditis, pericarditis, or multisystem inflammatory syndromes, was significantly higher in men than in women, with a higher frequency in adolescents than in adults. The inflammation-related AEs may require close monitoring and management in adolescents.
| S-EPMC9143867 | biostudies-literature
Project description:BACKGROUND:While clinical trials are considered the gold standard for detecting adverse events, often these trials are not sufficiently powered to detect difficult to observe adverse events. We developed a preliminary approach to predict 135 adverse events using post-market safety data from marketed drugs. Adverse event information available from FDA product labels and scientific literature for drugs that have the same activity at one or more of the same targets, structural and target similarities, and the duration of post market experience were used as features for a classifier algorithm. The proposed method was studied using 54 drugs and a probabilistic approach of performance evaluation using bootstrapping with 10,000 iterations. RESULTS:Out of 135 adverse events, 53 had high probability of having high positive predictive value. Cross validation showed that 32% of the model-predicted safety label changes occurred within four to nine years of approval (median: six years). CONCLUSIONS:This approach predicts 53 serious adverse events with high positive predictive values where well-characterized target-event relationships exist. Adverse events with well-defined target-event associations were better predicted compared to adverse events that may be idiosyncratic or related to secondary target effects that were poorly captured. Further enhancement of this model with additional features, such as target prediction and drug binding data, may increase accuracy.
| S-EPMC7191698 | biostudies-literature
Project description:BackgroundBlood transfusions are a vital component of modern healthcare, yet adverse reactions to blood product transfusions can cause morbidity, and rarely result in mortality. Therefore, accurate reporting of transfusion related adverse events (TRAEs) is paramount to improved transfusion practice. This study aims to investigate real-world data (RWD) on TRAEs by evaluating differences between ICD 9/10-based electronic health records (EHR) and blood bank-specific reporting.Study design and methodsTRAE data were retrospectively collected from a blood bank-specific database between Jan 2015 and June 2019 as the reference data source and compared it to ICD 9/10 diagnostic codes corresponding to various TRAEs. Seven reactions that have corresponding ICD 9/10 diagnostic codes were evaluated: Transfusion related circulatory overload (TACO), transfusion related acute lung injury (TRALI), febrile non-hemolytic reaction (FNHTR), transfusion-related anaphylactic reaction (TRA), acute hemolytic transfusion reaction (AHTR), delayed hemolytic transfusion reaction (DHTR), and delayed serologic reaction (DSTR). These accounted for 33% of the TRAEs at an academic institution during the study period.ResultsAmong 18637 adult blood transfusion recipients, there were 229 unique patients with 263 TRAE related ICD codes in the EHR, while there were 191 unique patients with 287 TRAEs identified in the blood bank database. None of the categories of reaction we investigated had perfect alignment between ICD 9/10 codes and blood bank specific diagnoses.DiscussionMultiple systemic challenges were identified that hinder effective reporting of TRAEs. Identifying factors causing inconsistent reporting between blood banks and EHRs is paramount to developing effective workability between these electronic systems, as well as across clinical and laboratory teams.
| S-EPMC9450944 | biostudies-literature
Project description:Carfilzomib was approved for the treatment of multiple myeloma in 2012 and since then there have been concerns for cardiovascular toxicity from its use. With this study, we aim to further study the hazards and underlying risk factors for cardiovascular adverse events associated with carfilzomib. This study was conducted using Surveillance, Epidemiology, and End Results (SEER)-Medicare data set of multiple myeloma from 2001 to 2015. Data were analyzed for hazards ratio of cardiovascular adverse events between carfilzomib users and nonusers. We identified 7330 patients with multiple myeloma of whom 815 were carfilzomib users. Carfilzomib users had a statistically significant hazard ratio of 1.41 with p < 0.0001 for all cardiovascular adverse events as compared to nonusers. Carfilzomib use was significantly associated with increased risk of heart failure (HR 1.47, p = 0.0002), ischemic heart disease (HR 1.45, p = 0.0002), and hypertension (HR 3.33, p < 0.0001), whereas there was no association between carfilzomib use and cardiac conduction disorders (arrhythmia and heart blocks). Carfilzomib users were at higher risk of new-onset edema (HR 5.09, p < 0.0001), syncope (HR 4.27, p < 0.0001), dyspnea (HR 1.33, p < 0.0001), and chest pain (HR 1.18, p < 0.0001) as compared to carfilzomib nonusers. Age above 75 years, preexisting cardiovascular disease, obesity, and twice a week carfilzomib schedule were significant risk factors associated with cardiovascular adverse events in carfilzomib users. The median time of the onset for all cardiovascular adverse events was 3.1 months. This study has identified a significantly higher likelihood of cardiovascular adverse events in elderly Medicare patients receiving carfilzomib.
| S-EPMC7826471 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.
| S-EPMC8263777 | biostudies-literature
Project description:Background: The role of antihypertensive drugs in inducing hyperuricaemia and gout has been a long-term concern in clinical practice. However, clinical studies regarding this issue are limited in number and have yielded inconsistent results. We comprehensively evaluated the association between various antihypertensive drugs and the occurrences of hyperuricaemia, gout and related adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS), aiming to guide the selection of antihypertensive drugs with a goal of minimizing the risk of hyperuricaemia, gout and related AEs. Methods: We used OpenVigil 2.1 to query the FAERS database. Hyperuricaemia, gout and related AEs were defined by 5 Preferred Terms: hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy. Disproportionality analysis was performed, and a positive signal indicated an association between AEs and antihypertensive drugs. Results: The numbers of antihypertensive drugs with positive signals for hyperuricaemia, gout, gouty arthritis, gouty tophus and urate nephropathy were 46, 66, 27, 8 and 6, respectively. These drugs included diuretics, antihypertensive drugs with central action, α blockers, β blockers, α and β blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, vasodilators, and compound preparations. Furthermore, 42 antihypertensive drugs had positive signal for more than one AEs. Conclusion: Our study suggests that some potassium-sparing diuretics, calcium channel blockers and losartan may be associated with increased risk of hyperuricaemia, gout or related AEs, which is inconsistent with most previous studies. Moreover, Our study also suggests that some antihypertensive drugs with central action, α and β blockers, renin inhibitors and vasodilators may be associated with increased risk of hyperuricaemia, gout or related AEs, which has not been reported in previous studies. These findings complement real-world evidence on the potential risks of hyperuricaemia, gout and related AEs associated with antihypertensive drugs.
| S-EPMC9868414 | biostudies-literature
Project description:In randomized clinical trials (RCTs) proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors showed a favorable safety profile, however, "real-world" data on adverse events (AEs) is scarce. Three datasets, a hospital registry (n = 164), and two Pharmacovigilance databases, Lareb (n = 149) and VigiLyze (n = 15,554), reporting AEs attributed to PCSK9 inhibitors (alirocumab or evolocumab) prescribed in clinical practice were analyzed. In the hospital registry, 41.5% of the patients reported any AE, most often injection-site reactions (33.8%) and influenza-like illness (27.9%). Twelve patients (7%) discontinued PCSK9 inhibitor treatment. Most common AE reported in the Lareb and VigiLyze database was myalgia (12.8% and 8.3%, respectively). No clinically relevant differences in gender or between drugs were observed. No specific subgroup of patients could be identified at risk of developing AEs. During follow-up, AEs resolved in most patients (71.1%). In a real-world setting, PCSK9 inhibitors are well tolerated with an overall safety profile comparable to RCTs.
| S-EPMC6704355 | biostudies-literature
Project description:IntroductionReal-world safety studies can provide important evidence on the thromboembolic risk associated with COVID-19 vaccines, considering that millions of people have been already vaccinated against COVID-19. In this study, we aimed to estimate the incidence of thromboembolic events after COVID-19 vaccination and to compare the Oxford-AstraZeneca vaccine with other COVID-19 vaccines.MethodsWe conducted a retrospective real-world safety study using data from two different data sources: the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza, RNF) and the Campania Region Health system (Sistema INFOrmativo saNità CampanIA, SINFONIA). From the start date of the COVID-19 vaccination campaign (27 December 2021) to 27 September 2022, information on COVID-19 vaccinations and thromboembolic events were extracted from the two databases. The reporting rate (RR) and its 95% confidence interval (95%CI) of thromboembolic events for 10,000 doses was calculated for each COVID-19 vaccine. Moreover, the odds of being vaccinated with the Oxford-AstraZeneca vaccine vs. the other COVID-19 vaccines in cases with thromboembolic events vs. controls without thromboembolic events were computed.ResultsA total of 12,692,852 vaccine doses were administered in the Campania Region, of which 6,509,475 (51.28%) were in females and mostly related to the Pfizer-BioNtech vaccine (65.05%), followed by Moderna (24.31%), Oxford-AstraZeneca (9.71%), Janssen (0.91%), and Novavax (0.02%) vaccines. A total of 641 ICSRs with COVID-19 vaccines and vascular events were retrieved from the RNF for the Campania Region, of which 453 (70.67%) were in females. Most ICSRs reported the Pfizer-BioNtech vaccine (65.05%), followed by Oxford-AstraZeneca (9.71%), Moderna (24.31%), and Janssen (0.91%). A total of 2451 events were reported in the ICSRs (3.8 events for ICSRs), of which 292 were thromboembolic events. The higher RRs of thromboembolic events were found with the Oxford-AstraZeneca vaccine (RR: 4.62, 95%CI: 3.50-5.99) and Janssen vaccine (RR: 3.45, 95%CI: 0.94-8.82). Thromboembolic events were associated with a higher likelihood of exposure to the Oxford-AstraZeneca vaccine compared to Pfizer-BioNtech (OR: 6.06; 95%CI: 4.22-8.68) and Moderna vaccines (OR: 6.46; 95%CI: 4.00-10.80).ConclusionWe observed a higher reporting of thromboembolic events with viral-vector-based vaccines (Oxford-AstraZeneca and Janssen) and an increased likelihood of being exposed to the Oxford-AstraZeneca vaccine compared to the mRNA vaccines (Pfizer-BioNtech and Moderna) among thromboembolic cases.
| S-EPMC10611339 | biostudies-literature
Project description:IntroductionStatistical signal detection is a crucial tool for rapidly identifying potential risks associated with pharmaceutical products. The unprecedented environment created by the coronavirus disease 2019 (COVID-19) pandemic for vaccine surveillance predisposes commonly applied signal detection methodologies to a statistical issue called the masking effect, in which signals for a vaccine of interest are hidden by the presence of other reported vaccines. This masking effect may in turn limit or delay our understanding of the risks associated with new and established vaccines.ObjectiveThe aim is to investigate the problem of masking in the context of COVID-19 vaccine signal detection, assessing its impact, extent, and root causes.MethodsBased on data underlying the Vaccine Adverse Event Reporting System, three commonly applied statistical signal detection methodologies, and a more advanced regression-based methodology, we investigate the temporal evolution of signals corresponding to five largely recognized adverse events and two potentially new adverse events.ResultsThe results demonstrate that signals of adverse events related to COVID-19 vaccines may be undetected or delayed due to masking when generated by methodologies currently utilized by pharmacovigilance organizations, and that a class of advanced methodologies can partially alleviate the problem. The results indicate that while masking is rare relative to all possible statistical associations, it is much more likely to occur in COVID-19 vaccine signaling, and that its extent, direction, impact, and roots are not static, but rather changing in accordance with the changing nature of data.ConclusionsMasking is an addressable problem that merits careful consideration, especially in situations such as COVID-19 vaccine safety surveillance and other emergency use authorization products.
| S-EPMC9219360 | biostudies-literature
Project description:Numerous drugs are currently under accelerated clinical investigation for the treatment of coronavirus disease 2019 (COVID-19); however, well-established safety and efficacy data for these drugs are limited. The goal of this study was to predict the potential of 25 small molecule drugs in clinical trials for COVID-19 to cause clinically relevant drug-drug interactions (DDIs), which could lead to potential adverse drug reactions (ADRs) with the use of concomitant medications. We focused on 11 transporters, which are targets for DDIs. In vitro potency studies in membrane vesicles or HEK293 cells expressing the transporters coupled with DDI risk assessment methods revealed that 20 of the 25 drugs met the criteria from regulatory authorities to trigger consideration of a DDI clinical trial. Analyses of real-world data from electronic health records, including a database representing nearly 120,000 patients with COVID-19, were consistent with several of the drugs causing transporter-mediated DDIs (e.g., sildenafil, chloroquine, and hydroxychloroquine). This study suggests that patients with COVID-19, who are often older and on various concomitant medications, should be carefully monitored for ADRs. Future clinical studies are needed to determine whether the drugs that are predicted to inhibit transporters at clinically relevant concentrations, actually result in DDIs.
| S-EPMC8217266 | biostudies-literature