Analysis Of Adverse Event Reports Research Articles

Drug risks associated with sarcopenia: a real-world and GWAS study

IntroductionDrug-induced sarcopenia has not received adequate attention. Meanwhile, there is growing recognition of the importance of effective pharmacovigilance in evaluating the benefits and risks of medications.AimsThe primary aim of this study is to investigate the potential association between drug use and sarcopenia through an analysis of adverse event reports from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and to evaluate the genetic factors contributing to drug-induced sarcopenia using summary-data-based Mendelian randomization (SMR).MethodsWe obtained reports of adverse drug reactions from FAERS. Primary outcomes included sarcopenia and potential sarcopenia. We calculated the Proportional reporting ratio (PRR) to assess the risk of specific adverse events associated with various drugs, applying chi-square tests for statistical significance. Additionally, we used SMR based on Genome-wide association study (GWAS) to evaluate the potential associations between drug target genes of some significant medications and sarcopenia outcomes. The outcome data for sarcopenia included metrics as hand grip strength and appendicular lean mass (ALM).ResultsA total of 55 drugs were identified as inducing potential sarcopenia, and 3 drugs were identified as inducing sarcopenia. The top 5 drugs causing a potential risk of sarcopenia were levofloxacin (PRR = 9.96, χ2 = 1057), pregabalin (PRR = 7.20, χ2 = 1023), atorvastatin (PRR = 4.68, χ2 = 903), duloxetine (PRR = 4.76, χ2 = 527) and venlafaxine (PRR = 5.56, χ2 = 504), and the 3 drugs that had been proved to induced sarcopenia included metformin (PRR = 7.41, χ2 = 58), aspirin (PRR = 5.93, χ2 = 35), and acetaminophen (PRR = 4.73, χ2 = 25). We identified electron-transfer flavoprotein dehydrogenase (ETFDH) and protein Kinase AMP-Activated Non-Catalytic Subunit Beta 1 (PRKAB1) as the primary drug target genes for metformin, while Prostaglandin-endoperoxide Synthase 1 (PTGS1) and Prostaglandin-endoperoxide Synthase 2 (PTGS2) were considered the primary action target genes for aspirin and acetaminophen according to DrugBank database. SMR showed that the expression abundance of ETFDH was negatively correlated with right hand grip strength (blood: OR = 1.01, p-value = 1.27e-02; muscle: OR = 1.01, p-value = 1.42e-02) and negatively correlated with appendicular lean mass (blood: OR = 1.03, p-value = 7.73e-08; muscle: OR = 1.03, p-value = 1.67e-07).ConclusionsWe find that metformin, aspirin, and acetaminophen are specifically noted for their potential to induce sarcopenia based on the analyses conducted. We perform signal mining for drug-associated sarcopenia events based on real-world data and provides certain guidance for the safe use of medications to prevent sarcopenia.

Cardiovascular adverse events associated with norepinephrine-dopamine reuptake inhibitors: a pharmacovigilance study of the FDA Adverse Event Reporting System.

Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR=4.2, 95% CI: 4.0-4.4) and hypertension (ROR=3.5, 95% CI: 3.3-3.7), while methylphenidate showed greater ROR for arrhythmias (ROR=2.8, 95% CI: 2.6-3.0) and palpitations (ROR=3.1, 95% CI: 2.9-3.3). Reboxetine had signals for palpitations (ROR=3.0, 95% CI: 2.8-3.2) and myocardial infarction (ROR=2.7, 95% CI: 2.5-2.9), whereas atomoxetine revealed signals for hypertension (ROR=2.9, 95% CI: 2.7-3.1) and syncope (ROR=2.5, 95% CI: 2.3-2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.

Safety assessment of asenapine in the FAERS database: real adverse event analysis and discussion on neurological and psychiatric side effects

PurposeThis study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders.MethodsEvent reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine.ResultsThe study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder.ConclusionAsenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.

Adverse Events Reporting in Digital Interventions Evaluations for Psychosis: A Systematic Literature Search and Individual Level Content Analysis of Adverse Event Reports.

Digital health interventions (DHIs) have significant potential to upscale treatment access to people experiencing psychosis but raise questions around patient safety. Adverse event (AE) monitoring is used to identify, record, and manage safety issues in clinical trials, but little is known about the specific content and context contained within extant AE reports. This study aimed to assess current AE reporting in DHIs. A systematic literature search was conducted by the iCharts network (representing academic, clinical, and experts by experience) to identify trials of DHIs in psychosis. Authors were invited to share AE reports recorded in their trials. A content analysis was conducted on the shared reports. We identified 593 AE reports from 18 DHI evaluations, yielding 19 codes. Only 29 AEs (4.9% of total) were preidentified by those who shared AEs as being related to the intervention or trial procedures. While overall results support the safety of DHIs, DHIs were linked to mood problems and psychosis exacerbation in a few cases. Additionally, 27% of studies did not report information on relatedness for all or at least some AEs; 9.6% of AE reports were coded as unclear because it could not be determined what had happened to participants. The results support the safety of DHIs, but AEs must be routinely monitored and evaluated according to best practice. Individual-level analyses of AEs have merit to understand safety in this emerging field. Recommendations for best practice reporting in future studies are provided.

Identifying new safety risk of human serum albumin: a retrospective study of real-world data.

Objective: To mine and analyze the adverse reaction signals of human serum albumin (HSA) using the FDA adverse event reporting system (FAERS) database for the safe clinical use of this drug. Methods: Data cleaning and analysis of adverse event reports in the FAERS database for a total of 76 quarters from Q1 2004 to Q4 2022 were performed using the reporting odds ratio (ROR), Medicines and Healthcare Products Regulatory Agency (MHRA), and Bayesian confidence propagation neural network (BCPNN). Gender-differentiated signal detection was used to investigate the gender differences in the occurrence of HSA adverse events. Results: Through a combination of three methods, a total of 535 adverse event reports were identified. These reports involved 1,885 cases of adverse reactions, with respiratory, thoracic, and mediastinal disorders, as well as general disorders and administration site conditions, as the most common. One noteworthy new signal was the occurrence of transfusion-related acute lung injury. Additionally, gender-differentiated signals were present, with females experiencing paraesthesia, hypertension, pulmonary oedema, loss of consciousness, and vomiting. Conclusion: This study has revealed that HSA poses a risk of causing transfusion-related acute lung injury. It has also been observed that adverse reactions, including paraesthesia, hypertension, pulmonary oedema, loss of consciousness, and vomiting, are more prevalent in females. These findings should be taken into account when using HSA in a clinical setting.

Analysis of Adverse Event Reports in FDA’s MAUDE Database

Background and Objective: Medical devices (MDs) play a pivotal role in the modern healthcare environment. Adverse events are an expected part of an MD’s lifecycle. To prevent the recurrence of such events, various vigilance systems have been established worldwide. The Manufacturer and User facility Device Experience (MAUDE) database of the US Food and Drug Administration (FDA) is a publicly accessible database that contains data of medical device reports (MDRs) submitted to FDA since 1991. The aim of this study is to examine the evolution of MD adverse event reports and analyze several characteristic parameters, as they evolved during the last three decades.
 Material and Methods: An analysis of MAUDE data was performed to examine the outcomes and device characteristics of adverse event reports from 1991 up to 11/2022. These outcomes included the event type, remedial action, report source, reporter occupation and device evaluation by manufacturer. Specific MD groups were analyzed separately to examine their effect on the event outcomes. Segregated files of the database that contain different types of information on adverse event reports were combined to investigate the various aspects of these reports.
 Results: Event outcomes are presented as annual histograms. An overall of about 15 million reports have been submitted to MAUDE during the 30 years period examined with more than 2.5 million of them during the first 10 months of the year 2022. This number is growing at an increasing rate. Most of the events (63.5%) have resulted in simple device malfunction, without serious implications to the patient. Depending on the device type however, the health risks may be higher (98.4% injuries from specific dental implants and 3.2% deaths from implantable defibrillators). About 20% of the reports have led to recalls or other corrective actions. Most of the reports (96%) are submitted by manufacturers and over 70% of the devices returned to them are evaluated, following the requirements of FDA 21 CFR, 803. The reporter’s occupation was found to be related to the types of devices associated with the event. Finally, the average device age was found to be 4 years, with an increasing tendency observed over the years, while still most of the events occur during the first year of operation.
 Conclusion: A medical device adverse event reporting system is a critical component of safety in the use of medical technology in modern healthcare. The information available in MAUDE and its use continues to grow at an accelerated rate and allows critical improvements of MDs, especially in terms of risk prevention, as it gives perception about their safety issues. FDA has taken various steps to encourage and facilitate adverse event reporting and make the data available to the public.

A Descriptive Analysis of Adverse Event Reports from the Quebec Cannabis Registry.

Published data on the safety of natural medical cannabis (MC) when used in the real-world clinical practice setting are lacking. This study aimed to describe adverse events (AEs) reported across three years following MC initiation. The Quebec Cannabis Registry (QCR) was a prospective registry of adults enrolled through participating physicians when they initiated MC between May 2015 and October 2018. Follow-up ended at MC discontinuation, loss to follow-up, three years, or end of data collection (May 2019). Data were collected at baseline and at follow-up visits every three months for the first two years, then once in the third year. Physicians filled adverse event (AE) reports, which were coded using MedDRA® preferred terms (PTs), and descriptive analyses were conducted. A total of 2991 patients were enrolled (mean age 50.9 years, 50.2% females). During follow-up, 108 patients (3.6%) experienced moderate or severe AEs, yielding 111 AE reports (three patients had two reports) and 214 AEs (average 1.9 AEs per report). Mild AEs were recorded as a reason for MC discontinuation for nine patients, but no AE reports were available. The most common PTs for ingested MC (62 reports) were dizziness (12.9%), nausea (11.3%), somnolence (9.7%), and vomiting (8.1%), and for inhaled MC (23 reports), headache (13.0%) was the most common. The most frequent PTs associated with tetrahydrocannabinol (THC)-dominant MC (25 reports) were dizziness and somnolence (12.0% each); for cannabidiol (CBD)-dominant MC (20 reports), vomiting (20.0%) was most common; and dizziness (17.2%), nausea (13.8%), somnolence (10.3%), and headache (8.6%) were the most frequent for balanced MC (58 reports). No new safety concerns were identified relative to the published literature, although notable differences in AE profile between modes of administration and cannabinoid content ratios should be considered by health professionals. Further work identifying and managing risk factors for AEs is warranted to maintain a favorable benefit-risk balance for MC.

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset.

Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine-topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration's FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs 'drug abuse', 'drug withdrawal syndrome', 'prescription drug used without a prescription', and 'intentional product use issue' were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine-topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine-topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Safety of equine tetanus antitoxin for prophylactic use in Ethiopia: a retrospective multi-center study

BackgroundTetanus remains a severe life-threatening infectious disease and neurological disorder in many parts of the world, where immunization programs are suboptimal. Any human injury or trauma has the possibility of getting infected with Clostridium tetani which is the sole causative bacterium of tetanus. Evidence is available that TAT may cause anaphylaxis and late serum sickness, while there has been no study conducted in Ethiopia. The Ethiopian Ministry of Health standard treatment guideline recommends tetanus prophylaxis for all tetanus-prone wounds. This study aimed to evaluate the safety of TAT administration in adults exposed to tetanus-prone wounds in Ethiopia.MethodsThe target product of this study was the equine tetanus antitoxin developed and manufactured by the ViNS Bioproducts Limited, India (Code: 130202084, A.W.No: 15/AAW/PI/02.00, DT: 25.04.2016). The product is delivered with the dose of 1000/1500 IU intramuscularly or subcutaneously to individuals at risk of tetanus infection for prophylactic purposes. The study was carried out in 11 healthcare facilities in Addis Ababa, Ethiopia, that had a relatively high clients load for tetanus-prone wounds. Medical records of patients with tetanus-prone wounds who received the equine TAT were reviewed retrospectively for any adverse events following immunization according to the World Health Organization (WHO) definition for adverse events following immunization (AEFI).ResultsThere were more than 20,000 patients treated for trauma in the facilities from 2015 to 2019. Upon revision of available registration books, we identified 6000 charts to be eligible for the study, of which 1213 charts that had complete and reliable data on the AEFI profile of the TAT were included in the final analysis. The median age of the study participants was 26 years (IQR = 11 years, age range: 18–91 years) and 78% (949) were male. The tetanus-prone wounds resulted mainly from stab (44%, 535) and blunt force (30%, 362), and the most common sites of wounds were hand (22%, 270) and head (21%, 253). The most and least frequently occurring types of wounds were open wounds (77%, 930) and organ system injury (0.003%, 4), respectively. The mean time of presenting at health facilities from the onset of trauma was 2.96 h. Of the total 1231 participants, one male participant who presented within 3 h after experiencing a wound on his nose at the workplace had a severe local reaction immediately after injection of the TAT. No AEFI was recorded for the other participants.ConclusionsThe adverse event following immunization of the equine tetanus antitoxin produced by the ViNS Bioproducts Limited was very rare. A regular review of the product’s safety performance and systematic collection and analysis of adverse event reports are important to ensure the safety of the product.

Shedding the Light on Post-Vaccine Myocarditis and Pericarditis in COVID-19 and Non-COVID-19 Vaccine Recipients.

Myocarditis and pericarditis have been linked recently to COVID-19 vaccines without exploring the underlying mechanisms, or compared to cardiac adverse events post-non-COVID-19 vaccines. We introduce an informatics approach to study post-vaccine adverse events on the systems biology level to aid the prioritization of effective preventive measures and mechanism-based pharmacotherapy by integrating the analysis of adverse event reports from the Vaccine Adverse Event Reporting System (VAERS) with systems biology methods. Our results indicated that post-vaccine myocarditis and pericarditis were associated most frequently with mRNA COVID-19 vaccines followed by live or live-attenuated non-COVID-19 vaccines such as smallpox and anthrax vaccines. The frequencies of cardiac adverse events were affected by vaccine, vaccine type, vaccine dose, sex, and age of the vaccinated individuals. Systems biology results suggested a central role of interferon-gamma (INF-gamma) in the biological processes leading to cardiac adverse events, by impacting MAPK and JAK-STAT signaling pathways. We suggest that increasing the time interval between vaccine doses minimizes the risks of developing inflammatory adverse reactions. We also propose glucocorticoids as preferred treatments based on system biology evidence. Our informatics workflow provides an invaluable tool to study post-vaccine adverse events on the systems biology level to suggest effective mechanism-based pharmacotherapy and/or suitable preventive measures.

Systematic Analysis of Adverse Event Reports for Sex Differences in Adverse Drug Events.

Increasing evidence has shown that sex differences exist in Adverse Drug Events (ADEs). Identifying those sex differences in ADEs could reduce the experience of ADEs for patients and could be conducive to the development of personalized medicine. In this study, we analyzed a normalized US Food and Drug Administration Adverse Event Reporting System (FAERS). Chi-squared test was conducted to discover which treatment regimens or drugs had sex differences in adverse events. Moreover, reporting odds ratio (ROR) and P value were calculated to quantify the signals of sex differences for specific drug-event combinations. Logistic regression was applied to remove the confounding effect from the baseline sex difference of the events. We detected among 668 drugs of the most frequent 20 treatment regimens in the United States, 307 drugs have sex differences in ADEs. In addition, we identified 736 unique drug-event combinations with significant sex differences. After removing the confounding effect from the baseline sex difference of the events, there are 266 combinations remained. Drug labels or previous studies verified some of them while others warrant further investigation.

Assessment of the impact of scheduled postmarketing safety summary analyses on regulatory actions.

In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities.

Identification of suicide-related events through network analysis of adverse event reports.

In the treatment of depression, it is essential to monitor for early warnings of suicide. The aim of this study was to identify the symptoms that would suggest a high suicide risk by analyzing data obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS) of selective serotonin reuptake inhibitors. Using FAERS reports from 1997 to the second quarter of 2012, we constructed the co-occurrence network of adverse events. From this network, we extracted the events that were strongly connected to suicidal events (suicidal attempts, suicidal ideation, suicidal behavior, and complete suicide) by means of the community detection method. We succeeded in obtaining a list of suicide-related adverse events. Owing to the randomness inherent in the algorithms of community detection, we found that the obtained list differed according to each trial of analysis. However, the lists we derived show considerable efficiency in identifying suicidal events. The network analysis appears to be a promising method for identifying signals of suicide.

Effective automated classification using ontology-based annotation: experience with analysis of adverse event reports

AERO OWL file: http://purl.obolibrary.org/obo/aero.owl Melanie Courtot: mcourtot@gmail.com Effective automated classification using ontology-based annotation: experience with analysis of adverse event reports Melanie Courtot1, Alan Ruttenberg2 , William W.L. Hsiao3, Fiona S.L. Brinkman4 and Ryan R. Brinkman1,5 1 BC Cancer Agency, Vancouver, BC, Canada, 2 School of Dental Medicine, University at Buffalo, Buffalo, NY, USA, 3 Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, 4 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada, 5 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

Cholinesterase Inhibitors and Pisa Syndrome: A Pharmacovigilance Study

Case reports suggest a relationship between cholinesterase inhibitors (ChEIs) and Pisa syndrome (PS), also known as pleurothotonus, a form of dystonia, but this relationship has not been systematically examined. Our objective was to estimate the adjusted reporting ratios of PS with donepezil, rivastigmine, and galantamine in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Retrospective analysis of adverse event reports in the FAERS database. Patients with drug-related adverse events in the FAERS database. The Gamma Poisson Shrinker algorithm was used to estimate the empirical Bayes geometric mean (EBGM) along with the lower and upper 90% confidence interval (CI) limits (EB05 and EB95, respectively), as measures of the adjusted reporting ratio of PS in patients taking ChEIs. EB05>2.0 was used as the cutoff for significance for the signals. The EBGM (EB05) was 37.9 (30) for all ChEIs, 25.6 (17.6) for donepezil, 76.4 (50.3) for galantamine, and 33.7 (21.2) for rivastigmine. All adverse event signals were strongly significant based on the a priori set EB05 cutoff. The female:male ratio in the reported cases was 2:1. No significant signals were found between ChEIs and other dystonias. About half of the ChEI users were also taking concomitant antipsychotics. Although FAERS data cannot establish causality due to reporting biases, our findings support a potential dopaminergic-cholinergic imbalance as an underlying mechanism for PS and may help increase clinician awareness, early identification, and treatment of ChEI-related dystonias.

Incidência de úlcera por pressão como indicador de qualidade na assistência de enfermagem

Objective: to analyze the incidence of pressure ulcers as a healthcare quality indicator at Coronel Frota Hospital in Porto Alegre. Method: a quantitative study based on the principles of exploration and description, which used statistical analysis of adverse event reports of pressure ulcers. Results: low pressure ulcer rates were identified. The affected patients had several risk factors including changes in nutrition, mobility and level of consciousness. The use of pyramidal mattress and the position change were highly indicated as nursing care in the prevention of pressure ulcers. Concluding Remarks: pressure ulcers developed despite the existence of preventive nursing care. The need to expand pressure ulcer prevention efforts and to evaluate the accuracy of adverse event reporting was identified

10‐Year Analysis of Adverse Event Reports to the Food and Drug Administration for Phosphodiesterase Type‐5 Inhibitors

To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective. We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years. Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology. The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths. Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers. Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270.

10-Year Analysis of Adverse Event Reports to the Food and Drug Administration for Phosphodiesterase Type-5 Inhibitors

10-Year Analysis of Adverse Event Reports to the Food and Drug Administration for Phosphodiesterase Type-5 Inhibitors

Pharmacovigilance analysis of adverse event reports for aliskiren hemifumarate, a first-in-class direct renin inhibitor

BackgroundThe purpose of this study was to examine the postmarketing safety profile of aliskiren hemifumarate, a first-in-class direct renin inhibitor.MethodsThe US Adverse Event Reporting System (AERS) was utilized to conduct a retrospective pharmacovigilance analysis by applying the Multi-item Gamma Poisson Shrinker data mining algorithm to calculate empiric Bayes geometric mean (EBGM) values of aliskiren-related adverse event reports. Reports received from January 2007 through December 2008 are included in this analysis.ResultsIn total, 1592 reports for aliskiren are identified in the AERS. Aliskiren was associated with reports of angioedema (EBGM 3.9, 95% confidence interval [CI] 3.2–4.7) and renal dysfunction (EBGM 3.4, 95% CI 2.6–4.5). Reports of hyperkalemia, dry cough, and diarrhea were also linked to aliskiren (EBGM 7.4, 95% CI 3.4–13.0, EBGM 11.0, 95% CI 7.8–14.2, EBGM 4.3, 95% CI 3.2–5.8, respectively).ConclusionAngioedema and renal dysfunction are potential adverse events associated with exposure to aliskiren. Patients with signs and symptoms of angioedema should stop aliskiren and seek urgent medical help. Aliskiren should not be used by patients with a risk of renal impairment. Additional studies are warranted to quantify further the risk of these events in patients with hypertension.

Mixed‐effects Poisson regression analysis of adverse event reports: The relationship between antidepressants and suicide

A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system.