Biclustering of adverse drug events in the FDA's spontaneous reporting system.
Ontology highlight
ABSTRACT:
SUBMITTER: Harpaz R
PROVIDER: S-EPMC3282185 | biostudies-literature | 2011 Feb
REPOSITORIES: biostudies-literature
Publications
Biclustering of adverse drug events in the FDA's spontaneous reporting system.
Harpaz R R Perez H H Chase H S HS Rabadan R R Hripcsak G G Friedman C C
Clinical pharmacology and therapeutics 20101229 2
In this article, we present a new pharmacovigilance data mining technique based on the biclustering paradigm, which is designed to identify drug groups that share a common set of adverse events (AEs) in the spontaneous reporting system (SRS) of the US Food and Drug Administration (FDA). A taxonomy of biclusters is developed, revealing that a significant number of bona fide adverse drug event (ADE) biclusters have been identified. Statistical tests indicate that it is extremely unlikely that the ...[more]
Similar Datasets
Project description:BackgroundIn Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database.MethodsWe included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.ResultsThe total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181-300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3-7.44), 2.61 (95% CI, 1.39-4.91), and 2.38 (95% CI, 1.04-5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62-351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35-14.77) and 6.99 (95% CI, 3.22-15.18). The β value of EB was 2.07 (95% CI, 1.48-2.76), which was classified as a wear-out failure type.ConclusionsFor MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.
| S-EPMC9241207 | biostudies-literature
Project description:BACKGROUND:Voluntary reports on adverse events (AEs) submitted by consumers have been facilitated through the MedWatch program in the United States (US), but few studies have described the characteristics of voluntary reports. OBJECTIVE:The aim of this study was to reveal the characteristics of current voluntary reports on AEs reported by consumers and healthcare professionals. METHODS:We performed analysis on voluntary reports of AEs in the US Food and Drug Administration AE Reporting System (FAERS) database submitted in 2016. We compared reports by consumers with those by healthcare professionals. RESULTS:The number of voluntary reports by consumers has increased since 2013 in the US. Reports by consumers were different from ones by health professionals in several important aspects such as demographics and outcomes of patients, AEs, and suspect drugs. The proportion of reports on female patients and on disability as a patient outcome were higher in reports by consumers than in those by healthcare professionals. Consumers more frequently reported concomitant drugs compared with healthcare professionals. Time to report varied among the occupations and depending on seriousness of outcomes. CONCLUSIONS:Our analysis of voluntary AE reports in the US FAERS database has shown that voluntary reports tended to include AEs related to subjective symptoms, as in some previous studies on patient reporting in the EU. Voluntary reports by consumers seemed to be different from ones by healthcare professionals in important aspects including demographics and reporting behaviors. These findings suggest that the heterogeneities should be addressed appropriately in using spontaneous reports.
| S-EPMC5984610 | biostudies-literature
Project description:PurposeThe purpose of this study was to investigate the adverse events (AEs) related to the use of off-label drugs.Materials and methodsA cross-sectional study was carried out using available data pertaining to off-label drug were sourced from U.S. FDA spontaneous adverse drug reaction reporting database (FAERS) and Korea Adverse Event Reporting System database (KIDS-KD) for the years 2014 to 2018. The number and frequencies of AE cases were calculated. Disproportionality was analyzed using the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the information component (IC), and the empirical Bayes geometric mean (EBGM) methods.ResultsThe reported AEs associated with off-label drug use were more common among older patients compared with younger patients. Gastric nonspecific symptoms and therapeutic procedure (4.16-4.57%) and haemorrage term (4.16-5.29%) were the most common AE symptoms and antithrombotic agents and immunosuppressants were the drugs most commonly reported to cause AEs in FAERS. Secondary term events (43.45-48.62%) including inappropriate schedule of drug administration and medication error were the most common AEs, and immunosuppressants and antipsychotics were the most common AE-related drugs from KIDS-KD. The numbers of reported AEs in new drug categories such as other antineoplastic agents trended to increase from 2014 to 2018 in both datasets.ConclusionThe numbers of reported AEs with off-label drug increased annually. AEs associated with off-label drugs may have a significant impact on older patients. Healthcare experts should be concerned about prescriptions of off-label drugs, especially anticoagulants and newly developed drugs such as immunosuppressants and antineoplastic agents.
| S-EPMC8387311 | biostudies-literature
Project description:Remdesivir was recommended for hospitalized patients with COVID-19. As already reported in the Summary of Product Characteristics, most of remdesivir's safety concerns are hepatoxicity and nephrotoxicity related. However, some cases have raised concerns regarding the potential cardiac events associated with remdesivir; therefore, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency requested to investigate all available data. Therefore, we analyzed all Individual Case Safety Reports (ICSRs) collected in the EudraVigilance database focusing on cardiac adverse events. From April to December 2020, 1375 ICSRs related to remdesivir were retrieved from EudraVigilance, of which 863 (62.8%) were related to male and (43.3%) adult patients. A total of 82.2% of all AEs (N = 2604) was serious and one third of the total ICSRs (N = 416, 30.3%) had a fatal outcome. The most frequently reported events referred to hepatic/hepatobiliary disorders (19.4%,), renal and urinary disorders (11.1%) and cardiac events (8.4%). Among 221 cardiac ICSRs, 69 reported fatal outcomes. Other drugs for cardiovascular disorders were reported as suspected/concomitant together with remdesivir in 166 ICSRs (75.1%), 62 of which were fatal. Moreover, the mean time to overall cardiac event was 3.3 days (±2.2). Finally, disproportionality analysis showed a two-fold increased risk of reporting a cardiac adverse event associated with remdesivir compared to both hydroxychloroquine and azithromycin. This study showed that remdesivir could be associated to risk of cardiac events, suggesting a potential safety signal which has not been completely evaluated yet. Further studies are needed to confirm these findings.
| S-EPMC8308754 | biostudies-literature
Project description:BackgroundAttitudes of healthcare professionals regarding spontaneous reporting of adverse drug reactions (ADRs) in Japan are not well known, and Japan's unique system of surveillance, called early post-marketing phase vigilance (EPPV), may affect these reporting attitudes. Our objectives were to describe potential effects of EPPV and to test whether ADR seriousness, prominence, and frequency are related to changes in reporting over time.MethodsA manufacturer's database of spontaneous ADR reports was used to extract data from individual case safety reports for 5 drugs subject to EPPV. The trend of reporting and the time lag between ADR onset and reporting to the manufacturer were examined. The following indices for ADRs occurring with each drug were calculated and analyzed to assess reporting trends: Serious:Non-serious ratio, High prominence:Low prominence ratio, and High frequency:Low frequency ratio.ResultsFor all 5 drugs, the time lag between ADR onset and reporting to the manufacturer was shorter in the EPPV period than in the post-EPPV period. All drugs showed higher Serious:Non-serious ratios in the post-EPPV period. No specific patterns were observed for the High prominence:Low prominence ratio. The High frequency:Low frequency ratio for peginterferon alpha-2a and sevelamer hydrochloride decreased steadily throughout the study period.ConclusionsHealthcare professionals may be more likely to report serious ADRs than to report non-serious ADRs, but the effect of event prominence on reporting trends is still unclear. Factors associated with ADR reporting attitude in Japan might be different from those in other countries because of EPPV and the involvement of medical representatives in the spontaneous reporting process. Pharmacovigilance specialists should therefore be cautious when comparing data between different time periods or different countries. Further studies are needed to elucidate the underlying mechanism of spontaneous ADR reporting in Japan.
| S-EPMC4416713 | biostudies-literature
Project description:PurposeTo describe the characteristics of adverse event reporting in the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) before and after the outbreak of the COVID-19 pandemic.MethodsWe included all FAERS reports from the US and Canada from November 7, 2019 to July 15, 2020 and divided the study period into three equal time intervals (pre-pandemic, first pandemic, second pandemic). We focused on methotrexate, a broadly used drug unrelated to COVID-19, and (hydroxy)chloroquine, another broadly used drug implicated in COVID-19 treatment. Using descriptive statistics, we compared reporting characteristics before and after the COVID-19 outbreak.ResultsDuring the study period, 366 998 cases (60% female, median age: 59 years) were submitted to FAERS. The daily median number of reports (1796 in the pre-pandemic, 1810 in the second pandemic time interval) and other characteristics remained stable. The daily median number of reports for methotrexate decreased from 28 in the pre-pandemic to 15 in the second pandemic time interval, with no considerable differences in other characteristics. The daily median number of reports for (hydroxy)chloroquine increased slightly from 1 in the pre-pandemic to 3 in the second pandemic time interval, while there were also changes in the demographics of cases and an increase in the proportion of cases reported by health professionals.ConclusionsThe overall reporting to FAERS did not change after the outbreak of the COVID-19 pandemic. However, some stimulated reporting was observed for (hydroxy)chloroquine, highlighting the need for caution when conducting pharmacovigilance analyses with substances related to COVID-19.
| S-EPMC8012989 | biostudies-literature
Project description:Spontaneous reporting systems may generate a large volume of information in real world conditions with a relatively low cost. Disproportionality measures are useful to indicate and quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality), based upon differences compared to the background reporting frequency. This cross-sectional study (2008 to 2013) aimed to analyse the feasibility of detecting such signals in the Brazilian Pharmacovigilance Database comprising suspected adverse drug reactions related to the use of doxorubicin, cyclophosphamide, carboplatin, trastuzumab, docetaxel, and paclitaxel for breast cancer chemotherapy. We first accessed overall database features (patient information and suspected adverse drug reactions) and further conducted a disproportionality analysis based on Reporting Odds Ratios with a confidence interval of 95% in order to identify possible signals of disproportionate reporting, only among serious suspected adverse drug reactions. Of all data reports of adverse reactions (n = 2603), 83% were classified as serious, with the highest prevalence with docetaxel (78.1%). The final analysis was performed using 1,309 reports with 3,139 drug-reaction pairs. The following signals of disproportionate reporting, some rare or not mentioned on labels, were observed: tachypnea with docetaxel; bronchospasm, syncope, cyanosis, and anaphylactic reaction with paclitaxel; and anaphylactic shock with trastuzumab. Structured management of spontaneous adverse drug reaction reporting is essential for monitoring the safe use of drugs and detecting early safety signals. Disproportionality signal analysis represents a viable and applicable strategy for oncology signal screening in the Brazilian Pharmacovigilance Database.
| S-EPMC6519311 | biostudies-literature
Project description:BackgroundAdverse drug reactions (ADRs) are undesired, unintended responses to drugs, and are significantly underreported. Pharmacists are drug experts recognized as custodians of drug safety, who are expected to be prepared for and knowledgeable about ADR reporting.ObjectivesTo identify Egyptian community pharmacists' preparedness for and perceived barriers to spontaneous ADR reporting.MethodsThis cross-sectional study recruited a sample of community pharmacists across Egypt, who were invited to complete a self-administrated questionnaire during April 2020.ResultsA total of 923 pharmacists across Egypt responded to the questionnaire. Most pharmacists were knowledgeable about the definition of ADRs (93.9 %) and indicated they felt reporting ADRs benefits the patients (82.2%). Despite recognizing their public health value, only a small percentage of participants conveyed familiarity with the reporting process for both paper (19.2%) and electronic (30.4%) forms, indeed 56.6% of participants did not remember what the ADR report form looked like. Moreover, 75.4% of respondents said they felt that community pharmacies are not the right place for reporting, with 49% suggesting that reporting was the responsibility of physicians. However, only 32.1% reported having insufficient time being a barrier to ADR reporting.ConclusionsCommunity pharmacists in Egypt are not well prepared for spontaneous ADR reporting due to a lack of knowledge about the formal process and not acknowledging their responsibility, although time was not a major barrier. Therefore, this highlights a clear opportunity for improvement likely involving targeted education.
| S-EPMC9315256 | biostudies-literature
Project description:BackgroundTaxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.MethodsTaxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson's χ2 test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).ResultsA total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05-6.88), PRR of 5.66, (χ2 = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55-14.14), PRR of 12.16 (χ2 = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).ConclusionsThe results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.
| S-EPMC8213312 | biostudies-literature
Project description:The efficacy and safety of herbal supplements suffer from challenges due to non-uniform representation of ingredient terms within biomedical and observational health data sources. The nature of how supplement data are reported within Spontaneous Reporting Systems (SRS) can limit analyses of supplement-associated adverse events due to the use of incorrect nomenclature or failing to identify herbs. This study aimed to extract, standardize, and summarize supplement-relevant reports from two SRSs: (1) Food and Drug Administration Adverse Event Reporting System (FAERS) and (2) Canada Vigilance Adverse Reaction (CVAR) database. A thesaurus of plant names was developed and integrated with a mapping and normalization approach that accommodated misspellings and variants. The reports gathered from FAERS between the years 2004 and 2016 show 185,915 herbal and 7,235,330 non-herbal accounting for 2.51%. The data from CVAR found 36,940 reports of herbal and 503,580 non-herbal reports between the years 1965 and 2017 for a total of 6.83%. Although not all cases were actual adverse events due to numerous variables and incomplete reporting, it is interesting to note that the herbs most frequently reported and significantly associated with adverse events were as follows: Avena sativa (Oats), Cannabis sativa (marijuana), Digitalis purpurea (foxglove), Humulus lupulus (hops), Hypericum perforatum (St John's Wort), Paullinia cupana (guarana), Phleum pretense (timothy-grass), Silybum marianum (milk thistle), Taraxacum officinale (Dandelion), and Valeriana officinalis (valerian). Using a scalable approach for mapping and resolution of herb names allowed data-driven exploration of potential adverse events from sources that have remained isolated in this specific area of research. The results from this study highlight several herb-associated safety issues providing motivation for subsequent in-depth analyses, including those that focus on the scope and severity of potential safety issues with supplement use.
| S-EPMC7297479 | biostudies-literature