Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database

Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database Nitin Kumar, Vivekanandan Kalaiselvan, Mandeep Kumar Arora This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4245237/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jul, 2024 Read the published version in European Journal of Clinical Pharmacology → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Monoclonal antibodies (mAbs), are pivotal in treating various diseases including cancers and autoimmune disorders. Despite their therapeutic benefits, mAbs therapy has been associated with neurological toxicity. Objectives: This study aimed to assess the incidence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases. Methods: A comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC 025 ), and Chi-Square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined. Results: The FAERS safety database contains 79,022 Individual Case Safety Reports (ICSRs) linking monoclonal antibodies (mAbs) to Nervous system disorders. Rituximab, Bevacizumab, Denosumab, Nivolumab, and Trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, Atezolizumab, Bevacizumab, and Trastuzumab showed strong drug-event associations. Signal Disproportionate Reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals. Conclusions: Interdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation. Monoclonal antibodies neurological toxicity FDA Adverse Event Reporting System Database (FAERS) signal detection disproportionality signal analysis Figures Figure 1 Figure 2 Figure 3 Introduction According to data compiled by the International Agency for Research on Cancer utilizing GLOBOCAN 2020 statistics, the global burden of cancer remains substantial, with an estimated 19.3 million new cases and 10 million deaths annually. Notably, the distribution of cancer cases worldwide is influenced by population density, with Eastern Asia bearing the highest burden, accounting for approximately 6 million new cases and 3.6 million deaths annually. Following Eastern Asia, Northern America ranks second in new cancer cases (2.6 million) but third in terms of deaths (0.699 million), trailing South-Central Asia (1.3 million deaths). Among cancers, breast cancer leads as the most commonly diagnosed malignancy, with 2.3 million cases annually, surpassing lung cancer. Subsequent prevalent cancers include lung, colon, prostate, and stomach cancers. Lung cancer remains the leading cause of cancer-related mortality, with an estimated 1.8 million deaths annually, followed by colorectal, stomach, liver, and female breast cancers [ 1 , 2 ]. In recent years, monoclonal antibody (mAb)-based immunotherapy has emerged as a pivotal component of cancer treatment alongside traditional modalities such as chemotherapy, radiotherapy, and surgery [ 3 ]. The advent of therapeutic antibodies has revolutionized targeted cancer therapy over the past three decades, starting with the development of the hybridoma technique in 1975 by Kohler & Milstein [ 4 ]. The subsequent humanization of antibodies pioneered by Greg Winter in 1988 has enabled the creation of therapeutic mAbs for diverse cancer types [ 5 ]. Despite their significant impact on healthcare, awareness of mAbs and their transformative role remains limited among the general population. Functionally, mAbs, derived from the billions of antibodies naturally produced by the immune system, exhibit specificity in binding to target antigens, thereby exerting cytotoxic effects through neutralization or pro-apoptotic mechanisms [ 6 ]. Moreover, mAbs can elicit innate immune responses, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC) [ 7 ]. A key mechanism of action involves blocking growth factor receptor signaling, exemplified by anti-EGFR mAbs like cetuximab, which disrupt pro-tumor signaling pathways [ 8 , 9 ]. The therapeutic landscape of mAbs has witnessed significant expansion since the approval of the first mAb, 'Muromonab-CD3' (Orthoclone Okt3), in 1986 for kidney transplant rejection. Presently, over 100 mAbs have received approval from regulatory authorities worldwide for treating various diseases, including colorectal cancer, non-Hodgkin lymphoma, breast cancer, and rheumatoid arthritis [ 10 ]. Additionally, mAbs are increasingly utilized across a spectrum of illnesses beyond oncology, spanning osteoporosis, multiple sclerosis, and metabolic disorders, among others [ 6 ]. The global market for monoclonal antibody therapy reached USD 237.61 billion in 2023, projected to exhibit a compound annual growth rate (CAGR) of 11.04% through 2030. This growth trajectory is attributed to continued research and development efforts aimed at innovating novel mAbs [ 11 ]. Notably, mAbs such as pembrolizumab, nivolumab, and rituximab are among the top-selling drugs in the oncology market, generating substantial revenue for the pharmaceutical industry [ 12 ]. However, despite their therapeutic efficacy, mAbs are associated with neurotoxicity, posing serious risks, particularly in cancer patients with comorbidities. Notable adverse neurological events have been reported with mAbs such as nivolumab, pembrolizumab, and bevacizumab, necessitating vigilant monitoring and management [ 13 ]. Pharmacovigilance databases like the FDA Adverse Event Reporting System (FAERS) play a pivotal role in post-marketing surveillance of mAbs and other pharmaceutical products [ 14 ]. FAERS, a comprehensive repository of real-world safety data, facilitates the identification of adverse reactions that may not have been captured during clinical trials. Its accessibility, extensive data coverage, and global reach make it an invaluable resource for healthcare stakeholders, aiding in the timely detection of safety signals and evaluation of medication risk-benefit profiles [ 15 , 16 ]. Against this backdrop, this research aims to characterize the safety profile of mAbs by analyzing FAERS data for potential safety signals and delineating the clinical features of involved Individual Case Safety Reports (ICSRs). Methods Sources of Data The present study utilized the FAERS database to conduct data mining of ICSRs pertaining to suspected ADR within the SOC 'Nervous System Disorders', with mAbs identified as the suspect drug. As of November 2023, the FAERS database contained over 27 million ICSRs, serving as a cornerstone for the FDA's post-marketing safety surveillance initiatives for medicinal and therapeutic biological products [ 17 ]. To facilitate our analysis, we identified and selected the top ten marketed monoclonal antibodies, as outlined in Table 1 [ 12 ]. Study Design: A cross-sectional observational study was undertaken utilizing a subset of the FAERS database encompassing reports of both serious and non-serious adverse events documented during the period of July 2023 (from initial authorization date to June 30, 2023) for the relevant pharmaceutical agents. Each ICSR included in the analysis was required to feature at least one mAbs drug among the suspected medications, coupled with at least one adverse event categorized under the SOC 'Nervous system disorders' according to standardized Medical Dictionary for Regulatory Activities (MedDRA) coding. Cases were extracted from the Line Listing (LL) retrieved from the safety database, specifically focusing on those where any of the following monoclonal antibodies were designated as Suspect Product Active Ingredients: Pembrolizumab, Nivolumab, Atezolizumab, Bevacizumab, Trastuzumab, Rituximab, Ipilimumab, Daratumumab, Denosumab, and Panitumumab. Instances involving suspected mAbs beyond these specified ones were categorized as non-cases. The analysis concentrated on adverse events pertaining to the SOC 'Nervous system disorders', utilizing Preferred Terms (PT) coded according to the latest version of the MedDRA hierarchy. Extracted Variables: During the course of this investigation, a line listing was generated from the FAERS database covering the period from the initial authorization date to June 30, 2023. The listing encompassed various parameters necessary for analysis, including patient demographics such as age at the time of the adverse event, gender, and weight. Additionally, product details were examined, encompassing suspect product active ingredients (suspected drugs), their trade names, indications for use, and concomitant medications. The focus of the analysis was on adverse reactions falling within the 'Nervous system disorders' SOC. Information extracted regarding adverse reactions included the name of the adverse drug reaction (Preferred Term name), event onset date, seriousness, as well as details regarding the reporter and case, such as reporter type, sender (the company submitting the case), manufacturer control number, manufacturer received date, case ID, case priority (whether expedited or non-expedited), country where the event occurred, and initial and latest FDA received dates for the case. Identifying duplicate case reports within the FAERS database posed a significant challenge due to submissions from various sources. Duplicate reports present a considerable obstacle in signal evaluation within the safety database [ 18 ]. Therefore, in this study, efforts were made to extract and remove duplicate case reports to ensure the authenticity of the data for subsequent analysis. Demonstrative assessment: A total of 30 Neurological events most number of reported cases were considered for evaluation and the remaining events fell into the "other neurological events" category. Safety data outline the medical characteristics of the cases with age, gender of patient, case seriousness, case priority, number of Co-suspect drugs, concomitant drugs, Type of reporter & name of country where event occurred with mAbs for better demonstration and evaluation of safety data. A ratio of fatality with the different mAbs in the extracted cases was evaluated. Cases with outcome of death (fatal) was considered and rest of the outcomes like hospitalization (initial/prolonged), disability, congenital anomaly (birth defect), required intervention (to prevent permanent implications) & other medically significant event outcomes including non-serious were considered in other cases, which assess the severity of cases. Statistical tools: A broad range of data evaluation approaches offered by quantitative signal detection. Several statistical data mining algorithms utilize in quantitative signal detection to compute the information from the safety databases. In this study disproportionality analysis was done for quantitative signal evaluation via three different tools i.e. Proportional Relative Risk (PRR), Information Component (IC 025 ) & Chi-Square Statistic (χ2). 1. The Proportional Relative Risk (PRR ≥ 2) : This signal generation technique is based on a proportionate approach that also takes into consideration the stability of large safety databases. For drugs of interest, this means calculating the proportion approach of certain reactions or groups of reactions, with all other drugs in the database contributing as the comparator. The PRR is the resultant value of these computations. PRR must be at least 2 or more than that to be deemed a signal [ 19 ]. Basically, the Two by Two table, which is displayed below (table-2), is used to calculate PRR [ 20 ]. Table 2 Calculation of PPR Target event All other events Total Target drug a b a + b All other drugs c d c + d Total a + c b + d a + b + c + d $$\mathbf{P}\mathbf{R}\mathbf{R}=\frac{\varvec{a}/\left(\varvec{a}+\varvec{b}\right)}{\varvec{c}/\left(\varvec{c}+\varvec{d}\right)}$$ Where , a: Number of cases for Target drug (mAb) with target event (specific Neurological event) b: Number of cases for Target drug (mAb) with other events (except target event) c: Number of cases for target event with all other drugs (except target mAb) d: Number of cases for all other drugs (except target mAb) with all other events (except target event) Which can be expressed as: The PRR is an easy-to-understand statistic that expresses every aspect of the increased risk of an ADR in the drug-exposed category over the drug-unexposed category [ 21 , 22 ]. $$\mathbf{P}\mathbf{R}\mathbf{R}=\frac{\mathbf{R}\mathbf{i}\mathbf{s}\mathbf{k} \mathbf{f}\mathbf{o}\mathbf{r} \mathbf{a}\mathbf{d}\mathbf{v}\mathbf{e}\mathbf{r}\mathbf{s}\mathbf{e} \mathbf{e}\mathbf{v}\mathbf{e}\mathbf{n}\mathbf{t} \mathbf{i}\mathbf{n} \mathbf{d}\mathbf{r}\mathbf{u}\mathbf{g}-\mathbf{E}\mathbf{x}\mathbf{p}\mathbf{o}\mathbf{s}\mathbf{e}\mathbf{d} \mathbf{c}\mathbf{a}\mathbf{t}\mathbf{e}\mathbf{g}\mathbf{o}\mathbf{r}\mathbf{y}}{ \mathbf{R}\mathbf{i}\mathbf{s}\mathbf{k} \mathbf{f}\mathbf{o}\mathbf{r} \mathbf{a}\mathbf{d}\mathbf{v}\mathbf{e}\mathbf{r}\mathbf{s}\mathbf{e} \mathbf{e}\mathbf{v}\mathbf{e}\mathbf{n}\mathbf{t} \mathbf{i}\mathbf{n} \mathbf{d}\mathbf{r}\mathbf{u}\mathbf{g}-\mathbf{U}\mathbf{n}\mathbf{e}\mathbf{x}\mathbf{p}\mathbf{o}\mathbf{s}\mathbf{e}\mathbf{d} \mathbf{c}\mathbf{a}\mathbf{t}\mathbf{e}\mathbf{g}\mathbf{o}\mathbf{r}\mathbf{y}}$$ 2. The Information Component (IC 025 ≥ 0) : The IC is a Bayesian tool to estimate the degree of the quantitative correlation between a target drug and a target event 22 . A positive Information Component (IC) indicates a stronger than predicted relationship between the drug and ADR; IC values which are negative or near zero, indicate no relationship at all. For this reason, we plan to examine the ICSRs for positive IC values. IC 025 value must be greater than or equals to zero (0) for considering a potential signal. As per Bate Et al. Logarithmic formula for the calculation of IC as follows [ 23 ]: $$\mathbf{I}\mathbf{C}=\mathbf{L}\mathbf{o}\mathbf{g}2\frac{\left[\mathbf{P} \left(\mathbf{x},\mathbf{y}\right)\right]}{\left[\mathbf{P}\left(\mathbf{x}\right)\mathbf{*}\varvec{P} \left(\varvec{y}\right)\right]}$$ Where P(x): probability of target drug (x) being mentioned in an ICSR. P(y): probability of a target ADR (y) being mentioned in an ICSR. P(x, y): probability of combination of target drug-ADR (x and y) being mentioned in an ICSR. In this study, we retrieved all these values from Microsoft excel as specified in Noren et al., which includes all the computations required for different IC values [ 24 ]. 3. The chi-square statistic (with 1 degree of freedom) (χ2 ≥ 4): Disproportionality analysis has traditionally relied on the use of the Chi-square statistical (χ2) tool. The dynamic nature of the data and the sequential scans of increasingly large amounts of data makes it essential to have computational ease of use. In EudraVigilance signal analysis, the Chi-square is used as an alternative measure of association between the medicinal product P and the adverse event R based on the following calculation [ 25 ]: $$\varvec{\chi }2=\frac{\left[\left(\mathbf{A}\mathbf{D}-\mathbf{B}\mathbf{C}\right)2\left(\mathbf{A}+\mathbf{B}+\mathbf{C}+\mathbf{D}\right)\right]}{\left[\left(\mathbf{A}+\mathbf{B}\right)\left(\mathbf{C}+\mathbf{D}\right)\left(\mathbf{A}+\mathbf{C}\right)\left(\mathbf{B}+\mathbf{D}\right)\right]}$$ Where A = Number of individual cases with the suspect medicinal product P involving an adverse event R. B = Number of individual cases related to the suspect medicinal product P, involving any other adverse events but R. C = Number of individual cases involving event R in relation to any other medicinal products but P. D = Number of individual cases involving any other adverse events but R and any other medicinal products but P. Results Characterization of cases A total of 79022 cases has been selected for analysis after exclusion of duplicate cases for the selected mAbs from the FAERS database as per the study period from the date of first authorization to June 30, 2023 of respective drugs and the events comes under the SOC 'Nervous system disorders.' Out of these 79022 cases, one of the most widely used mAbs, Rituximab, reported the highest number of cases: 23394 (29.60%), followed by the second highest number of cases reported for Bevacizumab 13441 (17.01%), for Denosumab 11095 (14.04%), for Nivolumab 8311 (10.50%), for Trastuzumab 7138 (9.03%), for Pembrolizumab 5331 (6.75%), for Ipilimumab 3803 (4.81%), for Atezolizumab 2677 (3.39%), Daratumumab 2239 (2.83%), and for Panitumumab 1593 (2.02%) (Figure: 1). These mAbs were prescribed to the patients for different indications i.e. Breast Cancer, Osteoporosis Postmenopausal, Rheumatoid Arthritis, Non-Small Cell Lung Cancer, Malignant Melanoma, Breast Cancer Metastatic, Diffuse Large B-Cell Lymphoma, Plasma Cell Myeloma, Colorectal Cancer Metastatic, Non-Hodgkin's Lymphoma, Colon Cancer, Lung Neoplasm Malignant, Metastatic Malignant Melanoma, B-Cell Lymphoma, Renal Cell Carcinoma etc. In this study PTs Headache, Neuropathy Peripheral, Dizziness, Hypoaesthesia, Paraesthesia Cerebrovascular Accident, Seizure, Syncope, Somnolence, Tremor & Loss of Consciousness respectively were providing highest number of cases associated with mAbs from safety database. As per the cumulative analysis of reported cases, most events occurred in the patient for the age group of 51–75 years old: 35121 cases (44.44%), followed by for 0–25 year olds: 1336 cases (1.69%), for 26–50 year olds: 9254 cases (11.71%), for ≥ 76 year olds: 9188 cases (11.63%), while in 24123 cases (30.53%), the age group was not specified (Table- 3). In total, 45073 (57.04%) cases for female patients, 23693 (29.98%) cases were reported for male patients, and in 10256 (12.98%) cases, gender was not specified (Table- 3). In terms of seriousness of cases, 67812 (85.81%) cases were reported as serious, while 11210 (14.19%) cases were non-serious. In terms of case priority, 67791 (85.79%) expedited cases, 10172 (12.87%) non-expedited cases, and 1059 (1.34%) cases of direct (sender 'Fda-Ctu') were reported. In 29542 (37.38%) cases none of patient was not taking any co-suspect drug, while in 17343 (21.95%) cases patients were taking only one co-suspect drug, in 9812 (12.42%) cases two co-suspect drugs, in 6812 (8.62%) cases three co-suspect drugs, in 4297 (5.44%) cases four co-suspect drugs and in 11216 (14.19%) cases patients were taking five or more than that co-suspect drugs. In total cases 50.79% patients were taking any of the concomitant drug while 49.21% cases one of patient were taking any concomitant drug these facts could play an important role in signal assessment. Majority of the cases were reported by health professionals 75.86% and 23.34% cases reported by Non-health professional, while 0.80% cases reported by unknown reporter. In 29.31% ICSRs country of incidence occurrence was reported as United states (US), in 63.97% ICSRs country of incidence occurrence were other countries (except US), while in 6.72% ICSRs country of incidence occurrence was not reported. In terms of seriousness of cases, 67812 (85.81%) cases were reported as serious with the reporting outcomes of hospitalization, life-threatening conditions, disability, fatality, required interventions, congenital anomalies, and other serious conditions, respectively, while 11210 (14.19%) cases were considered non-serious. The most serious cases were reported for Atezolizumab (96.97%), Rituximab (96.28%), and Bevacizumab (95.86%), respectively, while for Denosumab (30.37%), the least number of serious cases were reported (Figure-2). Disproportionality Signal Detection In this study, at least one from selected mAbs has shown significant statistical signal values, which meets all three criteria’s PRR, IC 025 & χ2 for signal detection. Thirty Drug-events pairs confirming with significant values to all three algorithms (Table-4). mAbs Panitumumab, Atezolizumab, Bevacizumab, Trastuzumab, Daratumumab & Denosumab sequencing were provided the highest number of satisfactory drug-events pairs with justifiable values in all the parameters. In term of analysis of PT, a total of 17 PTs shown a significant disproportionality conforming to the three algorithms. PTs Myasthenia Gravis, Neuropathy Peripheral, Peripheral Sensory Neuropathy & Polyneuropathy, Cerebral Infarction, Dysgeusia, Neurotoxicity & Sciatica have shown significant value with at least two or more than mAbs & while PTs Cerebral Haemorrhage, Cognitive Disorder, Encephalopathy, Lethargy, Memory Impairment, Migraine, Paraesthesia, Posterior Reversible Encephalopathy Syndrome & Taste Disorder were found satisfactory statistical values for all three algorithms with at least one mAb (Table-4). In a comparison to all mAb Panitumumab associated with Peripheral Sensory Neuropathy (PRR- 4.91, IC 025 - 0.34 & χ2- 296.27), Neurotoxicity (PRR- 4.69, IC 025 - 0.43 & χ2- 348.56), Polyneuropathy (PRR- 3.61, IC 025 - 0.38 & χ2- 236.75), Dysgeusia (PRR- 2.80, IC 025 - 0.04 & χ2- 58.34), & Neuropathy Peripheral (PRR- 3.18, IC 025 - 0.88 & χ2- 720.72); Atezolizumab associated with Encephalopathy (PRR- 2.06, IC 025 - 0.81 & χ2- 151.31), Cerebral Infarction (PRR- 2.17, IC 025 - 0.74 & χ2- 55.76), Myasthenia Gravis (PRR- 2.24, IC 025 - 0.74 & χ2- 46.80), & Peripheral Sensory Neuropathy (PRR- 2.33, IC 025 - 0.82 & χ2- 61.22); Bevacizumab associated with Cerebral Haemorrhage (PRR- 2.01, IC 025 - 0.58 & χ2- 120.02), Neurotoxicity (PRR- 2.28, IC 025 - 0.84 & χ2- 316.91), Peripheral Sensory Neuropathy (PRR- 2.68, IC 025 - 0.85 & χ2- 266.46), & Posterior Reversible Encephalopathy Syndrome (PRR- 3.03, IC 025 - 0.95 & χ2- 346.53); Daratumumab associated with Cognitive Disorder (PRR- 2.14, IC 025 - 0.20 & χ2- 32.78), Neuropathy Peripheral (PRR- 2.52, IC 025 - 1.00 & χ2- 493.21), & Polyneuropathy (PRR- 5.17, IC 025 - 1.39 & χ2- 738.89); Denosumab associated with Memory Impairment (PRR- 2.12, IC 025 - 0.58 & χ2- 198.95), Paraesthesia (PRR- 2.45, IC 025 - 0.85 & χ2- 766.85), & Sciatica (PRR- 2.67, IC 025 - 0.66 & χ2- 228.61), which shows highest number of drug-events pairs with satisfactory increased values of all included disproportionality algorithms in this study for a potential signal and rest of values have shown in the table-4. In this study it is found that 73 different Drug-ADR combinations (mAbs-Neurological disorders PTs) were showing at least two satisfactory disproportionality algorithmic values (IC 025 & χ2) which shown in below table-5. Additionally, the Ncomb (number of cases for specific drug-ADR combination) values of all the specific mAb and specific neurological PT were shown a significant positive result for disproportionality signal analysis as Ncomb ≥ 3 value is required for highlighting the potential signal for specific Drug-ADR combination [ 25 ], shown in Table-4 & Table-5. Discussion One of the next areas of cancer therapy is antibodies, which offer potent instruments for locating and acting on various antigens on tumors. Advances in enhancing the immune system's capacity to combat cancer will probably result in a greater utilization of medications like mAbs. mAbs therapies have provided more modern options as replacements for medications with a wide range of therapeutic uses & associated adverse events as well. Consequently, therapy associated neurotoxicity is something both neurological specialists and oncologists should be aware of, as thorough and methodical analysis of the various literature shown that neurotoxicity linked to mAbs in patients is not unusual [ 6 , 13 ]. In this study as well, it shown that huge number of cases for neurotoxicity associated with mAbs have been reported in the FAERS database. In a total of 79022 selected cases from the database, 85.81% of ICSRs were considered serious, with 14.06% of cases resulting in fatal outcomes. As per study conducted by Anthony S. et. al , Neurological events are one of the most frequent non-cardiac causes of sudden death; central nervous system (CNS) causes account for 15% of all non-cardiac deaths [ 26 ]. In this study, it was found that a major number of cases were reported for Rituximab, Bevacizumab, Denosumab, Nivolumab, Trastuzumab, Pembrolizumab, Ipilimumab, Atezolizumab, and Panitumumab, respectively, which were some of the most widely marketed and used mAbs [ 12 ]. As major number of cases were reported for female patients (54.07%), as these mAbs are widely used in reported indications such as breast cancer, osteoporosis postmenopausal, HER2 positive breast cancer, and ovarian cancer. As per literature data, these mAbs are recommended for targeting such binding sites as PD-L1 (programmed death receptor Ligand-1), HER2 (human epidermal growth factor receptor 2) and PD-1 (programmed death receptor 1) [ 3 ]. In male patients 29.98% cases were reported and in 12.98% of cases gender was not specified, according to some research, women are 1.5–1.7 times more likely than males to have serious ADRs [ 27 ]. As per this analysis found that most number of cases reported for the age group between 51–75 years old (44.44%), for 26–50-year-old 11.71%, for ≥ 76-year-old cases 11.63% and for 0-25-year-old only 1.69% cases were reported while in 30.53% cases age of the patients was not reported. As per Christopher Dodds (ed.), in general, there are various neurological disorders that are more likely to develop in the elderly population, i.e., Alzheimer’s disease, Parkinson’s disease, drug-induced dementia, strokes, and epilepsy [ 28 ]. Neurological disorders, which affecting 5–55% of those over the age of 55 years. A high risk of unfavorable health outcomes, such as death, disability, institutionalization as well as and hospitalization, is linked to them [ 29 ]. As per this study, it was also demonstrated that most cases were reported for PTs, i.e., headache, peripheral neuropathy, hypoaesthesia, paraesthesia cerebrovascular accident, seizure, syncope, somnolence, tremor & and loss of consciousness, which were specifically associated with mAbs. Literature reports also indicating for such type of events associated with mAbs, which are serious and lies up to grade-3-4 in term of severity of events [ 13 , 30 , 31 ]. In this study, disproportionality signal analysis suggesting a strong relationship between various mAbs and Neurological events as per the high rise in the statistical algorithmic values for PRR, IC 025 & χ2. Event Myasthenia Gravis with the significant values with four mAbs highest values for Pembrolizumab (PRR- 6.69, IC 025 - 0.85 & χ2- 1039.76), Nivolumab (PRR- 5.35, IC 025 - 0.97 & χ2- 811.74), Ipilimumab (PRR- 3.55, IC 025 - 0.56 & χ2- 236.95), and Atezolizumab (PRR- 2.24, IC 025 - 0.74 & χ2- 46.80) respectively, which are demonstrating the relatedness with each other. An autoimmune condition of the neuromuscular junctions, myasthenia gravis (MG) typically presents as fatigued weakness. It was mentioned in relation to a number of mAbs, including as Ipilimumab, Nivolumab, and Pembrolizumab [ 32 ]. Examples of myasthenia gravis caused by pembrolizumab obtained from Chinese and English databases that demonstrated a strong correlation [ 33 ]. During the disproportionality analysis, various similar events from neurological disorders have been shown significant values for multiple mAbs i.e. Polyneuropathy induced by Daratumumab (PRR- 5.17, IC 025 - 1.39 & χ2- 738.89) followed by Panitumumab (PRR- 3.61, IC 025 - 0.38 & χ2- 236.75) & Trastuzumab (PRR- 2.39, IC 025 - 0.42 & χ2- 239.39), similarly Neuropathy Peripheral induced by Panitumumab (PRR- 3.18, IC 025 - 0.88 & χ2- 720.72), followed by Daratumumab (PRR- 2.52, IC 025 - 1.00 & χ2- 493.21), Trastuzumab (PRR- 2.37, IC 025 - 0.78 & χ2- 1013.90) and Peripheral Sensory Neuropathy induced by Panitumumab, Bevacizumab, Atezolizumab & Trastuzumab as values shown in table-3 for the respective drug-event pairs. This association between these drug-events pairs as per the given statistical algorithms shown significant evidences for considering the potential signals. One typical negative effect of immunotherapies and biologic medicines is peripheral neuropathy [ 34 ]. A primarily sensory neuropathy can also be caused by Trastuzumab, which is used for treating HER-2-positive breast cancer that occurs in individuals who are not responding to conventional treatment [ 35 ]. Approximately, 36–53% patients have peripheral neuropathy, and 10–14% have severe cases [ 34 ]. Peripheral neuropathies may manifest either immediately or later in the therapeutic course. A brief follow-up shows generally positive results, sometimes even with mAb withdrawal alone. However, intravenous immunoglobulin or corticosteroids may be required to bring back and stabilize the illness. mAbs Atezolizumab, Nivolumab & Pembrolizumab used in the treatment of lung, renal cell, gastrointestinal, colorectal, uterine and breast cancer can lead to severe side effects that are Myasthenia Gravis (MG) most common which might cause the toxicity upto grade-5, other severe neurological disorders also have been reported in few articles like encephalopathy including the cases of Posterior reversible encephalopathy syndrome (PRES), Myopathy/myalgia, Headache, Peripheral neuropathy & seizures [ 13 ]. Additionally, in this study, we observed the optimum value of Ncomb for all the associated specific drug and specific event pairs, which showed significance values for PRR, IC025, and χ2, which is one more strong piece of algorithmic scientific evidence for potential signals, as the Ncomb values for all the significant drug-event pairs (potential signals) were more than or equal to three. There are no presumptions made with this strategy regarding the quantity of cases regarding a specific drug-ADR combination. When there were fewer drug-ADR combinations, the additional variation in the estimation of the association's intensity was managed [ 25 ]. It has been demonstrated that these statistical algorithmic techniques (Ncomb. PRR, IC 025 & χ2) are helpful in the regular process of detecting the signals. Because the quality of the data in the database affects the output's usefulness, this method should only be utilized to find signals—not to evaluate them. Clinical case evaluations step by step continue to be necessary for better assessment [ 25 ]. Strengths and Limitations Over 27 million (up to November-2023) ICSRs can be found in the FDA's FAERS database, which are supporting the FDA's post-marketing safety surveillance program for medicine and therapeutic biological products, the FAERS database is a constantly growing safety reports source. Regulatory authority guidelines are followed for safety reporting, and all reports are classified using terms from the Medical Dictionary for Regulatory Activities (MedDRA). Market authorization holders (MAH) are required by law to report any adverse events (AEs) to FAERS within 14 days of becoming aware of them, while consumers (patients, relatives, and advocates) and healthcare professionals (doctors, pharmacy professionals, and nurses) are free to submit AEs to FAERS. It is not necessary for the reports to be comprehensive, highly scientific, or supported by data [ 37 ]. ​Various types of safety reports that are available in the FAERS database allow the researcher to conduct a wide-spectrum analysis of a huge amount of safety data, resulting in different safety recommendations for drugs and events. Data from ICSRs that are spontaneously reported can be used to identify rare and serious adverse drug reactions (ADRs) that are difficult to find during clinical studies and also include data such as pediatric and geriatric populations. Data originated from our study of disproportionality signal analysis; it would be very helpful as a potential scientific evidence for further assessment of signals for these drug-event combinations, and this information plays an important role during treatment with monoclonal antibodies. It is an invaluable tool for physicians, authorities, and the pharmaceutical sector to quickly identify new correlations, evaluate the long-term risk-benefit profile of medications, and ultimately assist in the safe prescription of those medications [ 15 ]. There are several limitations on this study. Underreporting is the most well-known flaw in spontaneous reporting. During the evaluation of the results of this study, the role of the patient's underlying diseases, specific age, concomitant and co-suspect drugs, and many other variables were not listed separately in the cumulative line listing.​ Duplicate case reports in the safety database are a huge challenge in the signal evaluation process.​ Data mining techniques have a place, especially when dealing with enormous volumes of data, even while they cannot replace professional evaluation or make up for the inherent limits of a spontaneous reporting system [ 38 ]. Conclusions In conclusion, for mAbs Rituximab, Bevacizumab, Denosumab, Trastuzumab, and Pembrolizumab, the highest number of ADRs have been received in safety databases; a total of 85.81% of cases were serious, with 14.06% being fatal. As per this study, it was also demonstrated that most cases were reported for PTs, i.e., headache, peripheral neuropathy, hypoaesthesia, paraesthesia cerebrovascular accident, seizure, syncope, somnolence, tremors & and loss of consciousness, which were specifically associated with mAbs. In disproportionality signal analysis, we observed that many drug-event pairs showed significant statistical algorithmic values for PRR, IC025 and χ2, along with Ncomb values. Myasthenia gravis (MG) was associated with Pembrolizumab, Nivolumab, Ipilimumab, and Atezolizumab, polyneuropathy, and neuropathy. Peripheral neuropathy was associated with Daratumumab, Panitumumab, and Trastuzumab; peripheral sensory neuropathy was associated with Panitumumab, Bevacizumab, Atezolizumab, and Trastuzumab; and a few more important potential signals were also identified, i.e., Bevacizumab-induced neurotoxicity, posterior reversible encephalopathy syndrome and cerebral Haemorrhage, Atezolizumab-induced encephalopathy, Atezolizumab-induced cerebral infarction, denosumab-developed sciatica, memory impairment, and paraesthesia, and Daratumumab-induced cognitive disorder. One of the oldest mAbs, Rituximab-induced migraine and sciatica, and Trastuzumab-induced incduced lethargy and dysgeusia have been demonstrated to have an optimal association with each other for condensing them in the category of potential signals. It means these mAbs required more vigilant activities pertaining to the safety concerns of these mAbs while prescribing them to patients. Fatal outcome due to neurological diseases is not uncommon in cancer patients and hence, better collaboration between oncologists and neurologists is highly recommended. So, understanding the range, frequency, and severity of side effects while using medications as monotherapy or in conjunction with other therapeutic techniques is essential to minimizing morbidity and mortality. This is especially important given that antibody-mediated neurotoxicity is typically reversible. This study was really helpful in analyzing the safety profile of Monoclonal antibodies with respect to neurological disorders. Identified signals from disproportionality signal analysis during this study will play a significant role for further evaluation of risk-benefit profile of mAbs. Due to limitation of the data, more evaluation is required for these drug-events pairs for considering them as a confirmed signal. Declarations Funding No sources of funding were used for this study. Conflict of Interest The authors declare no conflict of interest. Availability of data and material study utilized the FAERS database to conduct data mining of ICSRs pertaining to suspected ADR. The public can access the FAERS databases. Thus, the encrypted data did not require approval from the FDA, which is in line with rules of ethics. Ethics approval Safety data retrieved from the spontaneous reporting process are anonymous and concur with ethical standards. Therefore, there was no further requirement for the ethical measure. Authors’ contributions NK wrote the original draft. MKA contributed to the conceptualization, methodology, review, and editing of the manuscript. VK contributed to the conceptualization, methodology and reviewed the manuscript. All authors approved the final version of the manuscript Informed consent Not applicable. References Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Znaor A et al (2021) Cancer statistics for the year 2020: An overview. 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No. Drugs Name (Brand Name) Marketing Company Year of Approval Indication 1 Pembrolizumab (Keytruda) Merck 2014 Primary mediastinal large B-cell lymphoma, Melanoma, NSCLC, Renal cell carcinoma, Cervical cancer, Classical HL, Urothelial carcinoma, Esophageal cancer, Gastric cancer, Hepatocellular carcinoma, Endometrial carcinoma, Merkel cell carcinoma. 2 Nivolumab (Opdivo) Bristo Myers Squibb 2014 Renal cell carcinoma, NSCLC, Gastroesophageal junction cancer, Malignant pleural mesothelioma, Classical HL, HNSCC, urothelial carcinoma, Hepatocellular carcinoma, CRC, Gastric cancer and Esophageal cancer 3 Atezolizumab (Tecentriq) Genentech 2016 NSCLC, Hepatocellular Carcinoma, Melanoma, Breast Cancer, Small Cell Lung Cancer and Bladder Cancer 4 Bevacizumab (Avastin) Genentech 2004 Ovarian Cancer, Colorectal Cancer, Fallopian Tube Cancer, Non-Small Cell Lung Cancer, Glioblastoma Multiforme, Peritoneal Cancer, Renal Cell Carcinoma, Cervical Cancer, Hepatocellular Carcinoma 5 Trastuzumab (Herceptin) Genentech 1998 Gastric Cancer, Breast Cancer 6 Rituximab (Rituxan) Genentech 1997 Rheumatoid Arthritis, Chronic Lymphocytic Leukemia, Pemphigus, Granulomatosis with Polyangiitis, Non-Hodgkin's Lymphoma Microscopic Polyangiitis 7 Ipilimumab (Yervoy) Bristol Myers Squibb 2011 Renal Cell Carcinoma, Melanoma, Colorectal Cancer, Malignant Pleural Mesothelioma, Non-Small Cell Lung Cancer, Hepatocellular Carcinoma 8 Daratumumab (Darzalex) Janssen Biotech 2015 Multiple Myeloma 9 Denosumab (Xgeva) Amgen 2010 Osteolytic Bone Lesions of Multiple Myeloma, Hypercalcemia of Malignancy, Osteolytic Bone Metastases of Solid Tumors, Giant Cell Tumor of Bone 10 Panitumumab (Vectibix) Amgen 2006 Colorectal Cancer NSCLC: Non-small cell lung cancer; Classical HL: Classical Hodgkin Lymphoma; CRC: Colorectal cancer; HNSCC: Head and neck squamous cell carcinoma Table- 3: Characterization of cases including at the minimum single Neurological adverse event with mAbs in FAERS (period: date of first authorization to 30-June-2023). Characteristics Name of Drugs Pembrolizumab ICSRs (n=5331) Nivolumab ICSRs (n=8311) Atezolizumab ICSRs (n=2677) Bevacizumab ICSRs (n=13441) Trastuzumab ICSRs (n=7138) Rituximab ICSRs (n=23394 Ipilimumab ICSRs (n=3803) Daratumumab ICSRs (n=2239) Denosumab ICSRs (n=11095) Panitumumab ICSRs (n=1593) Cumulative count Age (Years) ≤25 22 (0.41) 74 (0.89) 7 (0.26) 182 (1.35) 16 (0.22) 962 (4.11) 26 (0.68) 12 (0.54) 26 (0.23) 9 (0.56) 1336 (1.69) 26–50 367 (6.88) 862 (10.37) 214 (7.99) 1679 (12.49) 1546 (21.66) 3378 (14.44) 515 (13.54) 141 (6.30) 394 (3.55) 158 (9.92) 9254 (11.71) 51–75 2689 (50.44) 4456 (53.62) 1393 (52.04) 6409 (47.68) 2816 (39.45) 8584 (36.69) 2073 (54.51) 1043 (46.58) 4732 (42.65) 926 (58.13) 35121 (44.44) ≥ 76 775 (14.54) 1047 (12.60) 310 (11.58) 1197 (8.91) 270 (3.78) 1435 (6.13) 402 (10.57) 308 (13.76) 3286 (29.62) 158 (9.92) 9188 (11.63) Unknown 1478 (27.72) 1872 (22.52) 753 (28.13) 3974 (29.57) 2490 (34.88) 9035 (38.62) 787 (20.69) 735 (32.83) 2657 (23.95) 342 (21.47) 24123 (30.53) Gender Male (%) 2616 (49.07) 2787 (33.53) 1315 (49.12) 4946 (36.80) 298 (4.17) 6253 (26.73) 2279 (59.93) 1044 (46.63) 1319 (11.89) 836 (52.48) 23693 (29.98) Female (%) 2433 (45.64) 4956 (59.63) 1088 (40.64) 6678 (49.68) 6002 (84.09) 12015 (51.36) 1251 (32.90) 818 (36.53) 9242 (83.30) 590 (37.04) 45073 (57.04) Unknown/Not Specified 282 (5.29) 568 (6.83) 274 (10.24) 1817 (13.52) 838 (11.74) 5126 (21.91) 273 (7.18) 377 (16.84) 534 (4.81) 167 (10.48) 10256 (12.98) Case Seriousness Serious (%) 4802 (90.08) 7788 (93.71) 2596 (96.97) 12885 (95.86) 6644 (93.08) 22524 (96.28) 3576 (94.03) 2077 (92.76) 3406 (30.70) 1514 (95.04) 67812 (85.81) Non-serious (%) 529 (9.92) 523 (6.29) 81 (3.03) 556 (4.14) 494 (6.92) 870 (3.72) 227 (5.97) 162 (7.24) 7689 (69.30) 79 (4.96) 11210 (14.19) Case Priority Expedited 4230 (79.35) 7484 (90.05) 2563 (95.74) 12353 (91.91) 6510 (91.20) 22180 (94.81) 3435 (90.32) 1924 (85.93) 5966 (53.77) 1146 (71.94) 67791 (85.79) Non-Expedited 939 (17.61) 671 (8.07) 94 (3.51) 1012 (7.53) 605 (8.48) 1106 (4.73) 312 (8.20) 288 (12.86) 4699 (42.35) 446 (28.00) 10172 (12.87) Direct (sender 'Fda-Ctu') 162 (3.04) 156 (1.88) 20 (0.75) 76 (0.57) 23 (0.32) 108 (0.46) 56 (1.47) 27 (1.21) 430 (3.88) 1 (0.06) 1059 (1.34) Co-suspect drugs 0 (%) 2640 (49.52) 3835 (46.14) 713 (26.63) 3669 (27.30) 1508 (21.13) 6246 (26.70) 818 (21.51) 503 (22.47) 9007 (81.18) 603 (37.85) 29542 (37.38) 1 (%) 1452 (27.24) 3091 (37.19) 885 (33.06) 3523 (26.21) 1458 (20.43) 3321 (14.20) 2173 (57.14) 372 (16.61) 882 (7.95) 186 (11.68) 17343 (21.95) 2 (%) 746 (13.99) 721 (8.68) 460 (17.18) 2687 (19.99) 1442 (20.20) 2237 (9.56) 397 (10.44) 556 (24.83) 422 (3.80) 144 (9.04) 9812 (12.42) 3 (%) 210 (3.94) 361 (4.34) 368 (13.75) 1878 (13.97) 961 (13.46) 1714 (7.33) 250 (6.57) 466 (20.81) 208 (1.87) 396 (24.86) 6812 (8.62) 4 (%) 112 (2.10) 127 (1.53) 100 (3.74) 802 (5.97) 639 (8.95) 2054 (8.78) 76 (2.00) 125 (5.58) 147 (1.32) 115 (7.22) 4297 (5.44) ≥5 (%) 171 (3.21) 176 (2.12) 151 (5.64) 882 (6.56) 1130 (15.83) 7822 (33.44) 89 (2.34) 217 (9.69) 429 (3.87) 149 (9.35) 11216 (14.19) Concomitant drugs Taken 2147 (40.27) 3530 (42.47) 1457 (54.43) 7243 (53.89) 3978 (55.73) 12969 (55.44) 1639 (43.10) 1269 (56.68) 5050 (45.52) 855 (53.67) 40137 (50.79) Not taken 3184 (59.73) 4781 (57.53) 1220 (45.57) 6198 (46.11) 3160 (44.27) 10425 (44.56) 2164 (56.90) 970 (43.32) 6045 (54.48) 738 (46.33) 38885 (49.21) Type of reporter Health professional (%) 4139 (77.64) 6339 (76.27) 2501 (93.43) 11353 (84.47) 5777 (80.93) 19062 (81.48) 2998 (78.83) 1971 (88.03) 5692 (51.30) 116 (7.28) 59948 (75.86) Nonhealth professional (Consumer) (%) 1182 (22.17) 1962 (23.61) 174 (6.50) 1838 (13.67) 1273 (17.83) 4102 (17.53) 800 (21.04) 264 (11.79) 5370 (48.40) 1475 (92.59) 18440 (23.34) Unknown (%) 10 (0.2) 10 (0.12) 2 (0.07) 250 (1.86) 88 (1.23) 230 (0.98) 5 (0.13) 4 (0.18) 33 (0.30) 2 (0.13) 634 (0.80) Country where Event occurred US (%) 2029 (38.06) 2824 (33.98) 399 (14.90) 3971 (29.54) 1285 (18.00) 3811 (16.29) 1540 (40.49) 677 (30.24) 6457 (58.20) 168 (10.55) 23161 (23.31) Non-US (%) 3075 (57.68) 5429 (65.32) 1777 (66.38) 8089 (60.18) 5168 (72.40) 17311 (74.00) 2229 (58.61) 1552 (69.32) 4527 (40.80) 1395 (87.57) 50552 (63.97) Unknown (%) 227 (4.26) 58 (0.70) 501 (18.71) 1381 (10.27) 685 (9.60) 2272 (9.71) 34 (0.89) 10 (0.45) 111 (1.00) 30 (1.88) 5309 (6.72) Fatal Outcome 942 (17.67) 1555 (18.71) 473 (17.67) 2831 (21.06) 790 (11.07) 2951 (12.61) 602 (15.83) 269 (12.01) 685 (6.17) 16 (1.00) 11114 (14.06) Others outcome 4389 (82.33) 6756 (81.29) 2204 (82.33) 10610 (78.94) 6348 (88.93) 20443 (87.39) 3201 (84.17) 1970 (87.99) 10410 (93.83) 1577 (99.00) 67908 (85.94) Table-4: Satisfactory values for all three statistical algorithms (PRR, IC 025 , and χ2) for the safety reports of mAbs associated with PT of nervous system disorders (SOC) after disproportionality signal analysis extracted from FAERS safety database. Products (mAbs) Event (SOC= 'Nervous system disorders') Ncomb PRR IC 025 χ2 Atezolizumab Encephalopathy 282 2.06 0.81 151.31 Atezolizumab Cerebral Infarction 94 2.17 0.74 55.76 Atezolizumab Myasthenia Gravis 73 2.24 0.74 46.80 Atezolizumab Peripheral Sensory Neuropathy 86 2.33 0.82 61.22 Bevacizumab Cerebral Haemorrhage 336 2.01 0.58 120.02 Bevacizumab Neurotoxicity 506 2.58 0.84 316.91 Bevacizumab Peripheral Sensory Neuropathy 398 2.68 0.85 266.46 Bevacizumab Posterior Reversible Encephalopathy Syndrome 420 3.03 0.95 346.53 Daratumumab Cognitive Disorder 57 2.14 0.20 32.78 Daratumumab Neuropathy Peripheral 522 2.52 1.00 493.21 Daratumumab Polyneuropathy 249 5.17 1.39 738.89 Denosumab Memory Impairment 453 2.12 0.58 198.95 Denosumab Paraesthesia 1208 2.45 0.85 766.85 Denosumab Sciatica 317 2.67 0.66 228.61 Ipilimumab Myasthenia Gravis 152 3.55 0.56 236.95 Nivolumab Taste Disorder 263 2.80 0.54 227.25 Nivolumab Myasthenia Gravis 380 5.35 0.97 811.74 Panitumumab Dysgeusia 53 2.80 0.04 58.34 Panitumumab Neuropathy Peripheral 467 3.18 0.88 720.72 Panitumumab Polyneuropathy 132 3.61 0.38 236.75 Panitumumab Neurotoxicity 130 4.69 0.43 348.57 Panitumumab Peripheral Sensory Neuropathy 104 4.91 0.34 296.27 Pembrolizumab Cerebral Infarction 185 2.24 0.27 110.18 Pembrolizumab Myasthenia Gravis 322 6.69 0.85 1039.76 Rituximab Migraine 616 2.84 0.47 322.01 Rituximab Sciatica 569 2.93 0.46 310.99 Trastuzumab Neuropathy Peripheral 1445 2.37 0.78 1013.91 Trastuzumab Lethargy 219 2.38 0.27 141.28 Trastuzumab Polyneuropathy 364 2.39 0.42 239.39 Trastuzumab Dysgeusia 224 3.04 0.35 234.26 PT: Preferred Term; SOC: System Organ Class, mAb: Monoclonal antibodies; Ncomb: Number of cases for specific drug-ADR combination; PRR: Proportional Relative Risk; IC 025 : Information Component; χ2: Chi-square statistic; FAERS: FDA Adverse Event Reporting System. Table-5: Satisfactory values for 2 or more than two statistical algorithms (PRR, IC 025 , and χ2) for the safety reports of mAbs associated with PT of nervous system disorders (SOC) after disproportionality signal analysis extracted from FAERS safety database. Products (mAbs) Event (SOC= 'Nervous system disorders') Ncomb PRR IC 025 χ2 Atezolizumab Nervous System Disorder 66 1.99 0.56 30.66 Atezolizumab Encephalopathy 282 2.06 0.81 151.31 Atezolizumab Cerebral Infarction 94 2.17 0.74 55.76 Atezolizumab Myasthenia Gravis 73 2.24 0.74 46.80 Atezolizumab Peripheral Sensory Neuropathy 86 2.33 0.82 61.22 Bevacizumab Cerebrovascular Accident 739 1.44 0.31 79.80 Bevacizumab Encephalopathy 1044 1.63 0.46 198.49 Bevacizumab Cerebral Infarction 333 1.64 0.38 61.91 Bevacizumab Neuropathy Peripheral 1962 1.70 0.53 458.64 Bevacizumab Seizure 1043 1.97 0.64 361.14 Bevacizumab Cerebral Haemorrhage 336 2.01 0.58 120.02 Bevacizumab Neurotoxicity 506 2.58 0.84 316.91 Bevacizumab Peripheral Sensory Neuropathy 398 2.68 0.85 266.46 Bevacizumab Posterior Reversible Encephalopathy Syndrome 420 3.03 0.95 346.53 Daratumumab Tremor 108 1.47 0.13 16.31 Daratumumab Syncope 146 1.58 0.25 30.59 Daratumumab Cognitive Disorder 57 2.14 0.20 32.78 Daratumumab Neuropathy Peripheral 522 2.52 1.00 493.21 Daratumumab Polyneuropathy 249 5.17 1.39 738.89 Denosumab Neuralgia 240 1.65 0.30 48.59 Denosumab Tremor 412 1.14 0.01 6.35 Denosumab Migraine 214 1.39 0.12 19.29 Denosumab Dizziness 1416 1.44 0.34 167.88 Denosumab Cerebrovascular Accident 719 1.75 0.48 185.33 Denosumab Balance Disorder 336 1.79 0.39 91.34 Denosumab Hypoaesthesia 1066 1.92 0.61 373.73 Denosumab Memory Impairment 453 2.12 0.58 198.95 Denosumab Paraesthesia 1208 2.45 0.85 766.85 Denosumab Sciatica 317 2.67 0.66 228.61 Ipilimumab Cerebral Haemorrhage 89 1.64 0.06 20.92 Ipilimumab Myasthenia Gravis 152 3.55 0.56 236.95 Nivolumab Seizure 442 1.17 0.03 9.72 Nivolumab Cerebral Haemorrhage 161 1.37 0.04 14.06 Nivolumab Somnolence 374 1.45 0.20 46.35 Nivolumab Cerebral Infarction 228 1.77 0.25 63.02 Nivolumab Taste Disorder 263 2.80 0.54 227.25 Nivolumab Myasthenia Gravis 380 5.35 0.97 811.74 Panitumumab Dysgeusia 53 2.80 0.04 58.34 Panitumumab Neuropathy Peripheral 467 3.18 0.88 720.72 Panitumumab Polyneuropathy 132 3.61 0.38 236.75 Panitumumab Neurotoxicity 130 4.69 0.43 348.57 Panitumumab Peripheral Sensory Neuropathy 104 4.91 0.34 296.27 Pembrolizumab Somnolence 228 1.35 0.06 19.18 Pembrolizumab Taste Disorder 124 1.81 0.09 39.96 Pembrolizumab Cerebral Infarction 185 2.24 0.27 110.18 Pembrolizumab Myasthenia Gravis 322 6.69 0.85 1039.76 Rituximab Hypoaesthesia 1437 1.12 0.03 13.15 Rituximab Syncope 1126 1.22 0.08 30.91 Rituximab Dizziness 2570 1.26 0.15 94.85 Rituximab Tremor 913 1.28 0.10 36.42 Rituximab Nervous System Disorder 379 1.44 0.09 30.68 Rituximab Posterior Reversible Encephalopathy Syndrome 420 1.45 0.10 36.25 Rituximab Encephalopathy 1632 1.54 0.28 190.52 Rituximab Somnolence 1027 1.61 0.27 140.76 Rituximab Loss Of Consciousness 856 1.63 0.25 121.02 Rituximab Headache 5375 1.76 0.44 1155.80 Rituximab Amnesia 448 1.83 0.22 93.16 Rituximab Migraine 616 2.84 0.47 322.01 Rituximab Sciatica 569 2.93 0.46 310.99 Rituximab Neuralgia 439 1.52 0.13 46.66 Trastuzumab Dizziness 771 1.16 0.05 16.98 Trastuzumab Seizure 383 1.18 0.01 9.39 Trastuzumab Syncope 353 1.20 0.01 10.61 Trastuzumab Hypoaesthesia 542 1.38 0.17 53.43 Trastuzumab Taste Disorder 142 1.54 0.03 23.33 Trastuzumab Paraesthesia 576 1.58 0.28 109.58 Trastuzumab Tremor 380 1.71 0.26 99.03 Trastuzumab Neurotoxicity 223 1.79 0.17 66.49 Trastuzumab Peripheral Sensory Neuropathy 180 1.90 0.14 64.74 Trastuzumab Neuropathy Peripheral 1445 2.37 0.78 1013.91 Trastuzumab Lethargy 219 2.38 0.27 141.28 Trastuzumab Polyneuropathy 364 2.39 0.42 239.39 Trastuzumab Dysgeusia 224 3.04 0.35 30.66 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Jul, 2024 Read the published version in European Journal of Clinical Pharmacology → Version 1 posted Editorial decision: Revision requested 21 May, 2024 Reviews received at journal 21 May, 2024 Reviews received at journal 07 May, 2024 Reviewers agreed at journal 01 May, 2024 Reviewers agreed at journal 18 Apr, 2024 Reviewers invited by journal 18 Apr, 2024 Editor assigned by journal 15 Apr, 2024 Submission checks completed at journal 15 Apr, 2024 First submitted to journal 10 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4245237","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":291898279,"identity":"77a22253-235f-4d8a-a6c2-3e4b35a17d8f","order_by":0,"name":"Nitin Kumar","email":"","orcid":"","institution":"School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, Uttarakhand-248 009","correspondingAuthor":false,"prefix":"","firstName":"Nitin","middleName":"","lastName":"Kumar","suffix":""},{"id":291898280,"identity":"52c8c033-83e8-4463-b178-47e495e72413","order_by":1,"name":"Vivekanandan Kalaiselvan","email":"","orcid":"","institution":"National Coordination Centre, Indian Pharmacopoeia Commission","correspondingAuthor":false,"prefix":"","firstName":"Vivekanandan","middleName":"","lastName":"Kalaiselvan","suffix":""},{"id":291898281,"identity":"d4177070-bbc4-4118-a3dc-8a408e22fbc3","order_by":2,"name":"Mandeep Kumar Arora","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDADfvYGIGlgQYIWyZ4DIC0SJGgxuJEAoojQojvtdOLniop78gw3n1/d8KNAgoG/vTsBrxaz27mbJc+cKTZsnJ1TdrMH6DCJM2c3ENKyQbKxLYGxWTon7QYPUIuBRC5BLZt/ArXYt0meSbv5h0gt20C2JPZIsB+7Tawt2ywbziQkz+DJYbstYyDBQ4xfNt9sqEiw3X/8+LObb/7YyPG39+LXggR4DMAkscpBgP0BKapHwSgYBaNgBAEAulZK7XC6aTgAAAAASUVORK5CYII=","orcid":"","institution":"School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun, Uttarakhand-248 009","correspondingAuthor":true,"prefix":"","firstName":"Mandeep","middleName":"Kumar","lastName":"Arora","suffix":""}],"badges":[],"createdAt":"2024-04-10 05:32:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4245237/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4245237/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00228-024-03727-0","type":"published","date":"2024-07-25T16:16:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55060592,"identity":"5a907fab-45c8-4450-a8df-d388d7ba977e","added_by":"auto","created_at":"2024-04-22 02:30:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":9191,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of cases reported for each mAbs.\u003c/p\u003e","description":"","filename":"Onlinedrawingimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4245237/v1/c479a51efa396f19e649bf13.png"},{"id":55060167,"identity":"c263f5c7-9ba2-4c9e-9602-229a4f7a6bfa","added_by":"auto","created_at":"2024-04-22 02:22:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10996,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of serious \u0026amp; non-serious cases percentage reported for the mAbs.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the total cases cumulative rate of fatality was 14.06%, in which for the product Bevacizumab was highest (21.06%), for Nivolumab 18.71 %, for Atezolizumab 17.67%, for Pembrolizumab 17.67%, for Ipilimumab 15.83%, for Rituximab 12.61%, for Trastuzumab 11.07%, for Denosumab 6.17% and for the product Panitumumab (1%) lowest fatality rate was reported in ICSRs (Figure-3).\u003c/p\u003e","description":"","filename":"Onlinedrawingimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4245237/v1/699fe3207f1566aae3c9a4ac.png"},{"id":55060169,"identity":"83c34508-64c7-4abc-9d62-909a18198be1","added_by":"auto","created_at":"2024-04-22 02:22:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":11984,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of fatality rate in the reported ICSRs for mAbs\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinedrawingimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4245237/v1/83de3cc9c99755b04d36740d.png"},{"id":61596272,"identity":"d5708388-6096-47b8-b16a-7c4f4e2841d1","added_by":"auto","created_at":"2024-08-01 17:26:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1635833,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4245237/v1/91b321e0-ac45-4340-9141-87597c733480.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAccording to data compiled by the International Agency for Research on Cancer utilizing GLOBOCAN 2020 statistics, the global burden of cancer remains substantial, with an estimated 19.3\u0026nbsp;million new cases and 10\u0026nbsp;million deaths annually. Notably, the distribution of cancer cases worldwide is influenced by population density, with Eastern Asia bearing the highest burden, accounting for approximately 6\u0026nbsp;million new cases and 3.6\u0026nbsp;million deaths annually. Following Eastern Asia, Northern America ranks second in new cancer cases (2.6\u0026nbsp;million) but third in terms of deaths (0.699\u0026nbsp;million), trailing South-Central Asia (1.3\u0026nbsp;million deaths). Among cancers, breast cancer leads as the most commonly diagnosed malignancy, with 2.3\u0026nbsp;million cases annually, surpassing lung cancer. Subsequent prevalent cancers include lung, colon, prostate, and stomach cancers. Lung cancer remains the leading cause of cancer-related mortality, with an estimated 1.8\u0026nbsp;million deaths annually, followed by colorectal, stomach, liver, and female breast cancers [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn recent years, monoclonal antibody (mAb)-based immunotherapy has emerged as a pivotal component of cancer treatment alongside traditional modalities such as chemotherapy, radiotherapy, and surgery [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The advent of therapeutic antibodies has revolutionized targeted cancer therapy over the past three decades, starting with the development of the hybridoma technique in 1975 by Kohler \u0026amp; Milstein [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The subsequent humanization of antibodies pioneered by Greg Winter in 1988 has enabled the creation of therapeutic mAbs for diverse cancer types [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite their significant impact on healthcare, awareness of mAbs and their transformative role remains limited among the general population.\u003c/p\u003e \u003cp\u003eFunctionally, mAbs, derived from the billions of antibodies naturally produced by the immune system, exhibit specificity in binding to target antigens, thereby exerting cytotoxic effects through neutralization or pro-apoptotic mechanisms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Moreover, mAbs can elicit innate immune responses, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity (ADCC) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A key mechanism of action involves blocking growth factor receptor signaling, exemplified by anti-EGFR mAbs like cetuximab, which disrupt pro-tumor signaling pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e The therapeutic landscape of mAbs has witnessed significant expansion since the approval of the first mAb, 'Muromonab-CD3' (Orthoclone Okt3), in 1986 for kidney transplant rejection. Presently, over 100 mAbs have received approval from regulatory authorities worldwide for treating various diseases, including colorectal cancer, non-Hodgkin lymphoma, breast cancer, and rheumatoid arthritis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Additionally, mAbs are increasingly utilized across a spectrum of illnesses beyond oncology, spanning osteoporosis, multiple sclerosis, and metabolic disorders, among others [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe global market for monoclonal antibody therapy reached USD 237.61\u0026nbsp;billion in 2023, projected to exhibit a compound annual growth rate (CAGR) of 11.04% through 2030. This growth trajectory is attributed to continued research and development efforts aimed at innovating novel mAbs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Notably, mAbs such as pembrolizumab, nivolumab, and rituximab are among the top-selling drugs in the oncology market, generating substantial revenue for the pharmaceutical industry [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, despite their therapeutic efficacy, mAbs are associated with neurotoxicity, posing serious risks, particularly in cancer patients with comorbidities. Notable adverse neurological events have been reported with mAbs such as nivolumab, pembrolizumab, and bevacizumab, necessitating vigilant monitoring and management [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePharmacovigilance databases like the FDA Adverse Event Reporting System (FAERS) play a pivotal role in post-marketing surveillance of mAbs and other pharmaceutical products [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. FAERS, a comprehensive repository of real-world safety data, facilitates the identification of adverse reactions that may not have been captured during clinical trials. Its accessibility, extensive data coverage, and global reach make it an invaluable resource for healthcare stakeholders, aiding in the timely detection of safety signals and evaluation of medication risk-benefit profiles [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAgainst this backdrop, this research aims to characterize the safety profile of mAbs by analyzing FAERS data for potential safety signals and delineating the clinical features of involved Individual Case Safety Reports (ICSRs).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eSources of Data\u003c/h2\u003e\n \u003cp\u003eThe present study utilized the FAERS database to conduct data mining of ICSRs pertaining to suspected ADR within the SOC \u0026apos;Nervous System Disorders\u0026apos;, with mAbs identified as the suspect drug. As of November 2023, the FAERS database contained over 27\u0026nbsp;million ICSRs, serving as a cornerstone for the FDA\u0026apos;s post-marketing safety surveillance initiatives for medicinal and therapeutic biological products [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]. To facilitate our analysis, we identified and selected the top ten marketed monoclonal antibodies, as outlined in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Design:\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eA cross-sectional observational study was undertaken utilizing a subset of the FAERS database encompassing reports of both serious and non-serious adverse events documented during the period of July 2023 (from initial authorization date to June 30, 2023) for the relevant pharmaceutical agents. Each ICSR included in the analysis was required to feature at least one mAbs drug among the suspected medications, coupled with at least one adverse event categorized under the SOC \u0026apos;Nervous system disorders\u0026apos; according to standardized Medical Dictionary for Regulatory Activities (MedDRA) coding. Cases were extracted from the Line Listing (LL) retrieved from the safety database, specifically focusing on those where any of the following monoclonal antibodies were designated as Suspect Product Active Ingredients: Pembrolizumab, Nivolumab, Atezolizumab, Bevacizumab, Trastuzumab, Rituximab, Ipilimumab, Daratumumab, Denosumab, and Panitumumab. Instances involving suspected mAbs beyond these specified ones were categorized as non-cases. The analysis concentrated on adverse events pertaining to the SOC \u0026apos;Nervous system disorders\u0026apos;, utilizing Preferred Terms (PT) coded according to the latest version of the MedDRA hierarchy.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eExtracted Variables:\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eDuring the course of this investigation, a line listing was generated from the FAERS database covering the period from the initial authorization date to June 30, 2023. The listing encompassed various parameters necessary for analysis, including patient demographics such as age at the time of the adverse event, gender, and weight. Additionally, product details were examined, encompassing suspect product active ingredients (suspected drugs), their trade names, indications for use, and concomitant medications. The focus of the analysis was on adverse reactions falling within the \u0026apos;Nervous system disorders\u0026apos; SOC. Information extracted regarding adverse reactions included the name of the adverse drug reaction (Preferred Term name), event onset date, seriousness, as well as details regarding the reporter and case, such as reporter type, sender (the company submitting the case), manufacturer control number, manufacturer received date, case ID, case priority (whether expedited or non-expedited), country where the event occurred, and initial and latest FDA received dates for the case.\u003c/p\u003e\n \u003cp\u003eIdentifying duplicate case reports within the FAERS database posed a significant challenge due to submissions from various sources. Duplicate reports present a considerable obstacle in signal evaluation within the safety database [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. Therefore, in this study, efforts were made to extract and remove duplicate case reports to ensure the authenticity of the data for subsequent analysis.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eDemonstrative assessment:\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eA total of 30 Neurological events most number of reported cases were considered for evaluation and the remaining events fell into the \u0026quot;other neurological events\u0026quot; category.\u003c/p\u003e\n \u003cp\u003eSafety data outline the medical characteristics of the cases with age, gender of patient, case seriousness, case priority, number of Co-suspect drugs, concomitant drugs, Type of reporter \u0026amp; name of country where event occurred with mAbs for better demonstration and evaluation of safety data.\u003c/p\u003e\n \u003cp\u003eA ratio of fatality with the different mAbs in the extracted cases was evaluated. Cases with outcome of death (fatal) was considered and rest of the outcomes like hospitalization (initial/prolonged), disability, congenital anomaly (birth defect), required intervention (to prevent permanent implications) \u0026amp; other medically significant event outcomes including non-serious were considered in other cases, which assess the severity of cases.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical tools:\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eA broad range of data evaluation approaches offered by quantitative signal detection. Several statistical data mining algorithms utilize in quantitative signal detection to compute the information from the safety databases. In this study disproportionality analysis was done for quantitative signal evaluation via three different tools i.e. Proportional Relative Risk (PRR), Information Component (IC\u003csub\u003e025\u003c/sub\u003e) \u0026amp; Chi-Square Statistic (\u0026chi;2).\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cspan\u003e\u003cstrong\u003e1. The Proportional Relative Risk (PRR\u0026thinsp;\u0026ge;\u0026thinsp;2)\u003c/strong\u003e: This signal generation technique is based on a proportionate approach that also takes into consideration the stability of large safety databases. For drugs of interest, this means calculating the proportion approach of certain reactions or groups of reactions, with all other drugs in the database contributing as the comparator. The PRR is the resultant value of these computations. PRR must be at least 2 or more than that to be deemed a signal [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eBasically, the Two by Two table, which is displayed below (table-2), is used to calculate PRR [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCalculation of PPR\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTarget event\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll other events\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTarget drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll other drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv id=\"Equa\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e$$\\mathbf{P}\\mathbf{R}\\mathbf{R}=\\frac{\\varvec{a}/\\left(\\varvec{a}+\\varvec{b}\\right)}{\\varvec{c}/\\left(\\varvec{c}+\\varvec{d}\\right)}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eWhere\u003c/strong\u003e,\u003c/p\u003e\n \u003cp\u003ea: Number of cases for Target drug (mAb) with target event (specific Neurological event)\u003c/p\u003e\n \u003cp\u003eb: Number of cases for Target drug (mAb) with other events (except target event)\u003c/p\u003e\n \u003cp\u003ec: Number of cases for target event with all other drugs (except target mAb)\u003c/p\u003e\n \u003cp\u003ed: Number of cases for all other drugs (except target mAb) with all other events (except target event)\u003c/p\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eWhich can be expressed as: The PRR is an easy-to-understand statistic that expresses every aspect of the increased risk of an ADR in the drug-exposed category over the drug-unexposed category [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Equb\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e$$\\mathbf{P}\\mathbf{R}\\mathbf{R}=\\frac{\\mathbf{R}\\mathbf{i}\\mathbf{s}\\mathbf{k} \\mathbf{f}\\mathbf{o}\\mathbf{r} \\mathbf{a}\\mathbf{d}\\mathbf{v}\\mathbf{e}\\mathbf{r}\\mathbf{s}\\mathbf{e} \\mathbf{e}\\mathbf{v}\\mathbf{e}\\mathbf{n}\\mathbf{t} \\mathbf{i}\\mathbf{n} \\mathbf{d}\\mathbf{r}\\mathbf{u}\\mathbf{g}-\\mathbf{E}\\mathbf{x}\\mathbf{p}\\mathbf{o}\\mathbf{s}\\mathbf{e}\\mathbf{d} \\mathbf{c}\\mathbf{a}\\mathbf{t}\\mathbf{e}\\mathbf{g}\\mathbf{o}\\mathbf{r}\\mathbf{y}}{ \\mathbf{R}\\mathbf{i}\\mathbf{s}\\mathbf{k} \\mathbf{f}\\mathbf{o}\\mathbf{r} \\mathbf{a}\\mathbf{d}\\mathbf{v}\\mathbf{e}\\mathbf{r}\\mathbf{s}\\mathbf{e} \\mathbf{e}\\mathbf{v}\\mathbf{e}\\mathbf{n}\\mathbf{t} \\mathbf{i}\\mathbf{n} \\mathbf{d}\\mathbf{r}\\mathbf{u}\\mathbf{g}-\\mathbf{U}\\mathbf{n}\\mathbf{e}\\mathbf{x}\\mathbf{p}\\mathbf{o}\\mathbf{s}\\mathbf{e}\\mathbf{d} \\mathbf{c}\\mathbf{a}\\mathbf{t}\\mathbf{e}\\mathbf{g}\\mathbf{o}\\mathbf{r}\\mathbf{y}}$$\u003c/div\u003e\n \u003c/div\u003e\u003cspan\u003e\n \u003cp\u003e\u003cstrong\u003e2. The Information Component (IC\u003c/strong\u003e \u003csub\u003e\u0026nbsp;\u003cstrong\u003e025\u003c/strong\u003e\u0026nbsp;\u003c/sub\u003e\u0026thinsp;\u003cstrong\u003e\u0026ge;\u0026thinsp;0)\u003c/strong\u003e: The IC is a Bayesian tool to estimate the degree of the quantitative correlation between a target drug and a target event\u003csup\u003e22\u003c/sup\u003e. A positive Information Component (IC) indicates a stronger than predicted relationship between the drug and ADR; IC values which are negative or near zero, indicate no relationship at all. For this reason, we plan to examine the ICSRs for positive IC values. IC\u003csub\u003e025\u003c/sub\u003e value must be greater than or equals to zero (0) for considering a potential signal. As per Bate Et al. Logarithmic formula for the calculation of IC as follows [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]:\u003c/p\u003e\n \u003c/span\u003e\n \u003cdiv id=\"Equc\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e$$\\mathbf{I}\\mathbf{C}=\\mathbf{L}\\mathbf{o}\\mathbf{g}2\\frac{\\left[\\mathbf{P} \\left(\\mathbf{x},\\mathbf{y}\\right)\\right]}{\\left[\\mathbf{P}\\left(\\mathbf{x}\\right)\\mathbf{*}\\varvec{P} \\left(\\varvec{y}\\right)\\right]}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eWhere\u003c/p\u003e\n \u003cp\u003eP(x): probability of target drug (x) being mentioned in an ICSR.\u003c/p\u003e\n \u003cp\u003eP(y): probability of a target ADR (y) being mentioned in an ICSR.\u003c/p\u003e\n \u003cp\u003eP(x, y): probability of combination of target drug-ADR (x and y) being mentioned in an ICSR.\u003c/p\u003e\n \u003cp\u003eIn this study, we retrieved all these values from Microsoft excel as specified in Noren et al., which includes all the computations required for different IC values [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003cp\u003e\u003cstrong\u003e3. The chi-square statistic (with 1 degree of freedom) (\u0026chi;2\u0026thinsp;\u0026ge;\u0026thinsp;4):\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eDisproportionality analysis has traditionally relied on the use of the Chi-square statistical (\u0026chi;2) tool. The dynamic nature of the data and the sequential scans of increasingly large amounts of data makes it essential to have computational ease of use. In EudraVigilance signal analysis, the Chi-square is used as an alternative measure of association between the medicinal product P and the adverse event R based on the following calculation [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]:\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Equd\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equd\" name=\"EquationSource\"\u003e$$\\varvec{\\chi }2=\\frac{\\left[\\left(\\mathbf{A}\\mathbf{D}-\\mathbf{B}\\mathbf{C}\\right)2\\left(\\mathbf{A}+\\mathbf{B}+\\mathbf{C}+\\mathbf{D}\\right)\\right]}{\\left[\\left(\\mathbf{A}+\\mathbf{B}\\right)\\left(\\mathbf{C}+\\mathbf{D}\\right)\\left(\\mathbf{A}+\\mathbf{C}\\right)\\left(\\mathbf{B}+\\mathbf{D}\\right)\\right]}$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhere\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eA\u0026thinsp;=\u0026thinsp;Number of individual cases with the suspect medicinal product P involving an adverse event R.\u003c/p\u003e\n \u003cp\u003eB\u0026thinsp;=\u0026thinsp;Number of individual cases related to the suspect medicinal product P, involving any other adverse events but R.\u003c/p\u003e\n \u003cp\u003eC\u0026thinsp;=\u0026thinsp;Number of individual cases involving event R in relation to any other medicinal products but P.\u003c/p\u003e\n \u003cp\u003eD\u0026thinsp;=\u0026thinsp;Number of individual cases involving any other adverse events but R and any other medicinal products but P.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCharacterization of cases\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA total of 79022 cases has been selected for analysis after exclusion of duplicate cases for the selected mAbs from the FAERS database as per the study period from the date of first authorization to June 30, 2023 of respective drugs and the events comes under the SOC 'Nervous system disorders.' Out of these 79022 cases, one of the most widely used mAbs, Rituximab, reported the highest number of cases: 23394 (29.60%), followed by the second highest number of cases reported for Bevacizumab 13441 (17.01%), for Denosumab 11095 (14.04%), for Nivolumab 8311 (10.50%), for Trastuzumab 7138 (9.03%), for Pembrolizumab 5331 (6.75%), for Ipilimumab 3803 (4.81%), for Atezolizumab 2677 (3.39%), Daratumumab 2239 (2.83%), and for Panitumumab 1593 (2.02%) (Figure: 1). These mAbs were prescribed to the patients for different indications i.e. Breast Cancer, Osteoporosis Postmenopausal, Rheumatoid Arthritis, Non-Small Cell Lung Cancer, Malignant Melanoma, Breast Cancer Metastatic, Diffuse Large B-Cell Lymphoma, Plasma Cell Myeloma, Colorectal Cancer Metastatic, Non-Hodgkin's Lymphoma, Colon Cancer, Lung Neoplasm Malignant, Metastatic Malignant Melanoma, B-Cell Lymphoma, Renal Cell Carcinoma etc. In this study PTs Headache, Neuropathy Peripheral, Dizziness, Hypoaesthesia, Paraesthesia Cerebrovascular Accident, Seizure, Syncope, Somnolence, Tremor \u0026amp; Loss of Consciousness respectively were providing highest number of cases associated with mAbs from safety database.\u003c/p\u003e \u003cp\u003eAs per the cumulative analysis of reported cases, most events occurred in the patient for the age group of 51\u0026ndash;75 years old: 35121 cases (44.44%), followed by for 0\u0026ndash;25 year olds: 1336 cases (1.69%), for 26\u0026ndash;50 year olds: 9254 cases (11.71%), for \u0026ge;\u0026thinsp;76 year olds: 9188 cases (11.63%), while in 24123 cases (30.53%), the age group was not specified (Table- 3). In total, 45073 (57.04%) cases for female patients, 23693 (29.98%) cases were reported for male patients, and in 10256 (12.98%) cases, gender was not specified (Table- 3). In terms of seriousness of cases, 67812 (85.81%) cases were reported as serious, while 11210 (14.19%) cases were non-serious. In terms of case priority, 67791 (85.79%) expedited cases, 10172 (12.87%) non-expedited cases, and 1059 (1.34%) cases of direct (sender 'Fda-Ctu') were reported. In 29542 (37.38%) cases none of patient was not taking any co-suspect drug, while in 17343 (21.95%) cases patients were taking only one co-suspect drug, in 9812 (12.42%) cases two co-suspect drugs, in 6812 (8.62%) cases three co-suspect drugs, in 4297 (5.44%) cases four co-suspect drugs and in 11216 (14.19%) cases patients were taking five or more than that co-suspect drugs. In total cases 50.79% patients were taking any of the concomitant drug while 49.21% cases one of patient were taking any concomitant drug these facts could play an important role in signal assessment. Majority of the cases were reported by health professionals 75.86% and 23.34% cases reported by Non-health professional, while 0.80% cases reported by unknown reporter. In 29.31% ICSRs country of incidence occurrence was reported as United states (US), in 63.97% ICSRs country of incidence occurrence were other countries (except US), while in 6.72% ICSRs country of incidence occurrence was not reported.\u003c/p\u003e \u003cp\u003eIn terms of seriousness of cases, 67812 (85.81%) cases were reported as serious with the reporting outcomes of hospitalization, life-threatening conditions, disability, fatality, required interventions, congenital anomalies, and other serious conditions, respectively, while 11210 (14.19%) cases were considered non-serious. The most serious cases were reported for Atezolizumab (96.97%), Rituximab (96.28%), and Bevacizumab (95.86%), respectively, while for Denosumab (30.37%), the least number of serious cases were reported (Figure-2).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eDisproportionality Signal Detection\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this study, at least one from selected mAbs has shown significant statistical signal values, which meets all three criteria\u0026rsquo;s PRR, IC\u003csub\u003e025\u003c/sub\u003e \u0026amp; χ2 for signal detection. Thirty Drug-events pairs confirming with significant values to all three algorithms (Table-4). mAbs Panitumumab, Atezolizumab, Bevacizumab, Trastuzumab, Daratumumab \u0026amp; Denosumab sequencing were provided the highest number of satisfactory drug-events pairs with justifiable values in all the parameters. In term of analysis of PT, a total of 17 PTs shown a significant disproportionality conforming to the three algorithms. PTs Myasthenia Gravis, Neuropathy Peripheral, Peripheral Sensory Neuropathy \u0026amp; Polyneuropathy, Cerebral Infarction, Dysgeusia, Neurotoxicity \u0026amp; Sciatica have shown significant value with at least two or more than mAbs \u0026amp; while PTs Cerebral Haemorrhage, Cognitive Disorder, Encephalopathy, Lethargy, Memory Impairment, Migraine, Paraesthesia, Posterior Reversible Encephalopathy Syndrome \u0026amp; Taste Disorder were found satisfactory statistical values for all three algorithms with at least one mAb (Table-4).\u003c/p\u003e \u003cp\u003eIn a comparison to all mAb Panitumumab associated with Peripheral Sensory Neuropathy (PRR- 4.91, IC\u003csub\u003e025\u003c/sub\u003e- 0.34 \u0026amp; χ2- 296.27), Neurotoxicity (PRR- 4.69, IC\u003csub\u003e025\u003c/sub\u003e- 0.43 \u0026amp; χ2- 348.56), Polyneuropathy (PRR- 3.61, IC\u003csub\u003e025\u003c/sub\u003e- 0.38 \u0026amp; χ2- 236.75), Dysgeusia (PRR- 2.80, IC\u003csub\u003e025\u003c/sub\u003e- 0.04 \u0026amp; χ2- 58.34), \u0026amp; Neuropathy Peripheral (PRR- 3.18, IC\u003csub\u003e025\u003c/sub\u003e- 0.88 \u0026amp; χ2- 720.72); Atezolizumab associated with Encephalopathy (PRR- 2.06, IC\u003csub\u003e025\u003c/sub\u003e- 0.81 \u0026amp; χ2- 151.31), Cerebral Infarction (PRR- 2.17, IC\u003csub\u003e025\u003c/sub\u003e- 0.74 \u0026amp; χ2- 55.76), Myasthenia Gravis (PRR- 2.24, IC\u003csub\u003e025\u003c/sub\u003e- 0.74 \u0026amp; χ2- 46.80), \u0026amp; Peripheral Sensory Neuropathy (PRR- 2.33, IC\u003csub\u003e025\u003c/sub\u003e- 0.82 \u0026amp; χ2- 61.22); Bevacizumab associated with Cerebral Haemorrhage (PRR- 2.01, IC\u003csub\u003e025\u003c/sub\u003e- 0.58 \u0026amp; χ2- 120.02), Neurotoxicity (PRR- 2.28, IC\u003csub\u003e025\u003c/sub\u003e- 0.84 \u0026amp; χ2- 316.91), Peripheral Sensory Neuropathy (PRR- 2.68, IC\u003csub\u003e025\u003c/sub\u003e- 0.85 \u0026amp; χ2- 266.46), \u0026amp; Posterior Reversible Encephalopathy Syndrome (PRR- 3.03, IC\u003csub\u003e025\u003c/sub\u003e- 0.95 \u0026amp; χ2- 346.53); Daratumumab associated with Cognitive Disorder (PRR- 2.14, IC\u003csub\u003e025\u003c/sub\u003e- 0.20 \u0026amp; χ2- 32.78), Neuropathy Peripheral (PRR- 2.52, IC\u003csub\u003e025\u003c/sub\u003e- 1.00 \u0026amp; χ2- 493.21), \u0026amp; Polyneuropathy (PRR- 5.17, IC\u003csub\u003e025\u003c/sub\u003e- 1.39 \u0026amp; χ2- 738.89); Denosumab associated with Memory Impairment (PRR- 2.12, IC\u003csub\u003e025\u003c/sub\u003e- 0.58 \u0026amp; χ2- 198.95), Paraesthesia (PRR- 2.45, IC\u003csub\u003e025\u003c/sub\u003e- 0.85 \u0026amp; χ2- 766.85), \u0026amp; Sciatica (PRR- 2.67, IC\u003csub\u003e025\u003c/sub\u003e- 0.66 \u0026amp; χ2- 228.61), which shows highest number of drug-events pairs with satisfactory increased values of all included disproportionality algorithms in this study for a potential signal and rest of values have shown in the table-4.\u003c/p\u003e \u003cp\u003eIn this study it is found that 73 different Drug-ADR combinations (mAbs-Neurological disorders PTs) were showing at least two satisfactory disproportionality algorithmic values (IC\u003csub\u003e025\u003c/sub\u003e \u0026amp; χ2) which shown in below table-5.\u003c/p\u003e \u003cp\u003eAdditionally, the Ncomb (number of cases for specific drug-ADR combination) values of all the specific mAb and specific neurological PT were shown a significant positive result for disproportionality signal analysis as Ncomb\u0026thinsp;\u0026ge;\u0026thinsp;3 value is required for highlighting the potential signal for specific Drug-ADR combination [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], shown in Table-4 \u0026amp; Table-5.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOne of the next areas of cancer therapy is antibodies, which offer potent instruments for locating and acting on various antigens on tumors. Advances in enhancing the immune system's capacity to combat cancer will probably result in a greater utilization of medications like mAbs. mAbs therapies have provided more modern options as replacements for medications with a wide range of therapeutic uses \u0026amp; associated adverse events as well. Consequently, therapy associated neurotoxicity is something both neurological specialists and oncologists should be aware of, as thorough and methodical analysis of the various literature shown that neurotoxicity linked to mAbs in patients is not unusual [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study as well, it shown that huge number of cases for neurotoxicity associated with mAbs have been reported in the FAERS database. In a total of 79022 selected cases from the database, 85.81% of ICSRs were considered serious, with 14.06% of cases resulting in fatal outcomes. As per study conducted by \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAnthony S. et. al\u003c/span\u003e, Neurological events are one of the most frequent non-cardiac causes of sudden death; central nervous system (CNS) causes account for 15% of all non-cardiac deaths [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, it was found that a major number of cases were reported for Rituximab, Bevacizumab, Denosumab, Nivolumab, Trastuzumab, Pembrolizumab, Ipilimumab, Atezolizumab, and Panitumumab, respectively, which were some of the most widely marketed and used mAbs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. As major number of cases were reported for female patients (54.07%), as these mAbs are widely used in reported indications such as breast cancer, osteoporosis postmenopausal, HER2 positive breast cancer, and ovarian cancer. As per literature data, these mAbs are recommended for targeting such binding sites as PD-L1 (programmed death receptor Ligand-1), HER2 (human epidermal growth factor receptor 2) and PD-1 (programmed death receptor 1) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In male patients 29.98% cases were reported and in 12.98% of cases gender was not specified, according to some research, women are 1.5\u0026ndash;1.7 times more likely than males to have serious ADRs [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs per this analysis found that most number of cases reported for the age group between 51\u0026ndash;75 years old (44.44%), for 26\u0026ndash;50-year-old 11.71%, for \u0026ge;\u0026thinsp;76-year-old cases 11.63% and for 0-25-year-old only 1.69% cases were reported while in 30.53% cases age of the patients was not reported. As per Christopher Dodds (ed.), in general, there are various neurological disorders that are more likely to develop in the elderly population, i.e., Alzheimer\u0026rsquo;s disease, Parkinson\u0026rsquo;s disease, drug-induced dementia, strokes, and epilepsy [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeurological disorders, which affecting 5\u0026ndash;55% of those over the age of 55 years. A high risk of unfavorable health outcomes, such as death, disability, institutionalization as well as and hospitalization, is linked to them [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs per this study, it was also demonstrated that most cases were reported for PTs, i.e., headache, peripheral neuropathy, hypoaesthesia, paraesthesia cerebrovascular accident, seizure, syncope, somnolence, tremor \u0026amp; and loss of consciousness, which were specifically associated with mAbs. Literature reports also indicating for such type of events associated with mAbs, which are serious and lies up to grade-3-4 in term of severity of events [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn this study, disproportionality signal analysis suggesting a strong relationship between various mAbs and Neurological events as per the high rise in the statistical algorithmic values for PRR, IC\u003csub\u003e025\u003c/sub\u003e \u0026amp; χ2. Event Myasthenia Gravis with the significant values with four mAbs highest values for Pembrolizumab (PRR- 6.69, IC\u003csub\u003e025\u003c/sub\u003e- 0.85 \u0026amp; χ2- 1039.76), Nivolumab (PRR- 5.35, IC\u003csub\u003e025\u003c/sub\u003e- 0.97 \u0026amp; χ2- 811.74), Ipilimumab (PRR- 3.55, IC\u003csub\u003e025\u003c/sub\u003e- 0.56 \u0026amp; χ2- 236.95), and Atezolizumab (PRR- 2.24, IC\u003csub\u003e025\u003c/sub\u003e- 0.74 \u0026amp; χ2- 46.80) respectively, which are demonstrating the relatedness with each other. An autoimmune condition of the neuromuscular junctions, myasthenia gravis (MG) typically presents as fatigued weakness. It was mentioned in relation to a number of mAbs, including as Ipilimumab, Nivolumab, and Pembrolizumab [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Examples of myasthenia gravis caused by pembrolizumab obtained from Chinese and English databases that demonstrated a strong correlation [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDuring the disproportionality analysis, various similar events from neurological disorders have been shown significant values for multiple mAbs i.e. Polyneuropathy induced by Daratumumab (PRR- 5.17, IC\u003csub\u003e025\u003c/sub\u003e- 1.39 \u0026amp; χ2- 738.89) followed by Panitumumab (PRR- 3.61, IC\u003csub\u003e025\u003c/sub\u003e- 0.38 \u0026amp; χ2- 236.75) \u0026amp; Trastuzumab (PRR- 2.39, IC\u003csub\u003e025\u003c/sub\u003e- 0.42 \u0026amp; χ2- 239.39), similarly Neuropathy Peripheral induced by Panitumumab (PRR- 3.18, IC\u003csub\u003e025\u003c/sub\u003e- 0.88 \u0026amp; χ2- 720.72), followed by Daratumumab (PRR- 2.52, IC\u003csub\u003e025\u003c/sub\u003e- 1.00 \u0026amp; χ2- 493.21), Trastuzumab (PRR- 2.37, IC\u003csub\u003e025\u003c/sub\u003e- 0.78 \u0026amp; χ2- 1013.90) and Peripheral Sensory Neuropathy induced by Panitumumab, Bevacizumab, Atezolizumab \u0026amp; Trastuzumab as values shown in table-3 for the respective drug-event pairs. This association between these drug-events pairs as per the given statistical algorithms shown significant evidences for considering the potential signals.\u003c/p\u003e \u003cp\u003eOne typical negative effect of immunotherapies and biologic medicines is peripheral neuropathy [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. A primarily sensory neuropathy can also be caused by Trastuzumab, which is used for treating HER-2-positive breast cancer that occurs in individuals who are not responding to conventional treatment [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Approximately, 36\u0026ndash;53% patients have peripheral neuropathy, and 10\u0026ndash;14% have severe cases [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Peripheral neuropathies may manifest either immediately or later in the therapeutic course. A brief follow-up shows generally positive results, sometimes even with mAb withdrawal alone. However, intravenous immunoglobulin or corticosteroids may be required to bring back and stabilize the illness.\u003c/p\u003e \u003cp\u003emAbs Atezolizumab, Nivolumab \u0026amp; Pembrolizumab used in the treatment of lung, renal cell, gastrointestinal, colorectal, uterine and breast cancer can lead to severe side effects that are Myasthenia Gravis (MG) most common which might cause the toxicity upto grade-5, other severe neurological disorders also have been reported in few articles like encephalopathy including the cases of Posterior reversible encephalopathy syndrome (PRES), Myopathy/myalgia, Headache, Peripheral neuropathy \u0026amp; seizures [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, in this study, we observed the optimum value of Ncomb for all the associated specific drug and specific event pairs, which showed significance values for PRR, IC025, and χ2, which is one more strong piece of algorithmic scientific evidence for potential signals, as the Ncomb values for all the significant drug-event pairs (potential signals) were more than or equal to three. There are no presumptions made with this strategy regarding the quantity of cases regarding a specific drug-ADR combination. When there were fewer drug-ADR combinations, the additional variation in the estimation of the association's intensity was managed [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt has been demonstrated that these statistical algorithmic techniques (Ncomb. PRR, IC\u003csub\u003e025\u003c/sub\u003e \u0026amp; χ2) are helpful in the regular process of detecting the signals. Because the quality of the data in the database affects the output's usefulness, this method should only be utilized to find signals\u0026mdash;not to evaluate them. Clinical case evaluations step by step continue to be necessary for better assessment [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eOver 27\u0026nbsp;million (up to November-2023) ICSRs can be found in the FDA's FAERS database, which are supporting the FDA's post-marketing safety surveillance program for medicine and therapeutic biological products, the FAERS database is a constantly growing safety reports source. Regulatory authority guidelines are followed for safety reporting, and all reports are classified using terms from the Medical Dictionary for Regulatory Activities (MedDRA). Market authorization holders (MAH) are required by law to report any adverse events (AEs) to FAERS within 14 days of becoming aware of them, while consumers (patients, relatives, and advocates) and healthcare professionals (doctors, pharmacy professionals, and nurses) are free to submit AEs to FAERS. It is not necessary for the reports to be comprehensive, highly scientific, or supported by data [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. ​Various types of safety reports that are available in the FAERS database allow the researcher to conduct a wide-spectrum analysis of a huge amount of safety data, resulting in different safety recommendations for drugs and events. Data from ICSRs that are spontaneously reported can be used to identify rare and serious adverse drug reactions (ADRs) that are difficult to find during clinical studies and also include data such as pediatric and geriatric populations. Data originated from our study of disproportionality signal analysis; it would be very helpful as a potential scientific evidence for further assessment of signals for these drug-event combinations, and this information plays an important role during treatment with monoclonal antibodies. It is an invaluable tool for physicians, authorities, and the pharmaceutical sector to quickly identify new correlations, evaluate the long-term risk-benefit profile of medications, and ultimately assist in the safe prescription of those medications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThere are several limitations on this study. Underreporting is the most well-known flaw in spontaneous reporting. During the evaluation of the results of this study, the role of the patient's underlying diseases, specific age, concomitant and co-suspect drugs, and many other variables were not listed separately in the cumulative line listing.​ Duplicate case reports in the safety database are a huge challenge in the signal evaluation process.​ Data mining techniques have a place, especially when dealing with enormous volumes of data, even while they cannot replace professional evaluation or make up for the inherent limits of a spontaneous reporting system [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn conclusion, for mAbs Rituximab, Bevacizumab, Denosumab, Trastuzumab, and Pembrolizumab, the highest number of ADRs have been received in safety databases; a total of 85.81% of cases were serious, with 14.06% being fatal. As per this study, it was also demonstrated that most cases were reported for PTs, i.e., headache, peripheral neuropathy, hypoaesthesia, paraesthesia cerebrovascular accident, seizure, syncope, somnolence, tremors \u0026amp; and loss of consciousness, which were specifically associated with mAbs.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn disproportionality signal analysis, we observed that many drug-event pairs showed significant statistical algorithmic values for PRR, IC025 and χ2, along with Ncomb values. Myasthenia gravis (MG) was associated with Pembrolizumab, Nivolumab, Ipilimumab, and Atezolizumab, polyneuropathy, and neuropathy. Peripheral neuropathy was associated with Daratumumab, Panitumumab, and Trastuzumab; peripheral sensory neuropathy was associated with Panitumumab, Bevacizumab, Atezolizumab, and Trastuzumab; and a few more important potential signals were also identified, i.e., Bevacizumab-induced neurotoxicity, posterior reversible encephalopathy syndrome and cerebral Haemorrhage, Atezolizumab-induced encephalopathy, Atezolizumab-induced cerebral infarction, denosumab-developed sciatica, memory impairment, and paraesthesia, and Daratumumab-induced cognitive disorder.\u003c/p\u003e \u003cp\u003eOne of the oldest mAbs, Rituximab-induced migraine and sciatica, and Trastuzumab-induced incduced lethargy and dysgeusia have been demonstrated to have an optimal association with each other for condensing them in the category of potential signals. It means these mAbs required more vigilant activities pertaining to the safety concerns of these mAbs while prescribing them to patients.\u003c/p\u003e \u003cp\u003eFatal outcome due to neurological diseases is not uncommon in cancer patients and hence, better collaboration between oncologists and neurologists is highly recommended. So, understanding the range, frequency, and severity of side effects while using medications as monotherapy or in conjunction with other therapeutic techniques is essential to minimizing morbidity and mortality. This is especially important given that antibody-mediated neurotoxicity is typically reversible.\u003c/p\u003e \u003cp\u003eThis study was really helpful in analyzing the safety profile of Monoclonal antibodies with respect to neurological disorders. Identified signals from disproportionality signal analysis during this study will play a significant role for further evaluation of risk-benefit profile of mAbs. Due to limitation of the data, more evaluation is required for these drug-events pairs for considering them as a confirmed signal.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo sources of funding were used for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003estudy utilized the FAERS database to conduct data mining of ICSRs pertaining to suspected ADR.\u0026nbsp;The public can access the FAERS databases. Thus, the encrypted data did not require approval from the FDA, which is in line with rules of ethics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSafety data retrieved from the spontaneous reporting process are anonymous and concur with ethical standards. Therefore, there was no further requirement for the ethical measure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e NK wrote the original draft. MKA contributed to the conceptualization, methodology,\u003c/p\u003e\n\u003cp\u003ereview, and editing of the manuscript. VK contributed to the conceptualization, methodology and reviewed the manuscript. All authors approved the final version of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Znaor A et al (2021) Cancer statistics for the year 2020: An overview. Int J Cancer 149(4):778\u0026ndash;789. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ijc.33588\u003c/span\u003e\u003cspan address=\"10.1002/ijc.33588\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Cancer Med 12(3):3365\u0026ndash;3375. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/cam4.5062\u003c/span\u003e\u003cspan address=\"10.1002/cam4.5062\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable- 1: List of approved mAbs\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e\u003cstrong\u003eS. No.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrugs Name (Brand Name)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarketing Company\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear of Approval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003ePembrolizumab (Keytruda)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eMerck\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003ePrimary mediastinal large B-cell lymphoma, Melanoma, NSCLC, Renal cell carcinoma, Cervical cancer, Classical HL, Urothelial carcinoma, Esophageal cancer, Gastric cancer, Hepatocellular carcinoma, Endometrial carcinoma, Merkel cell carcinoma.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eNivolumab (Opdivo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eBristo Myers Squibb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eRenal cell carcinoma, NSCLC, Gastroesophageal junction cancer, Malignant pleural mesothelioma, Classical HL, HNSCC, urothelial carcinoma, Hepatocellular carcinoma, CRC, Gastric cancer and Esophageal cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eAtezolizumab (Tecentriq)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eGenentech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eNSCLC, Hepatocellular Carcinoma, Melanoma,\u0026nbsp;Breast Cancer, Small Cell Lung Cancer and\u0026nbsp;Bladder Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eBevacizumab (Avastin)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eGenentech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eOvarian Cancer, Colorectal Cancer, Fallopian Tube Cancer, Non-Small Cell Lung Cancer, Glioblastoma Multiforme, Peritoneal Cancer, Renal Cell Carcinoma, Cervical Cancer, Hepatocellular Carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eTrastuzumab (Herceptin)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eGenentech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e1998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eGastric Cancer, Breast Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eRituximab (Rituxan)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eGenentech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eRheumatoid Arthritis, Chronic Lymphocytic Leukemia, Pemphigus, Granulomatosis with Polyangiitis, Non-Hodgkin\u0026apos;s Lymphoma Microscopic Polyangiitis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eIpilimumab (Yervoy)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eBristol Myers Squibb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eRenal Cell Carcinoma, Melanoma, Colorectal Cancer, Malignant Pleural Mesothelioma, Non-Small Cell Lung Cancer, Hepatocellular Carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eDaratumumab (Darzalex)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eJanssen Biotech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eMultiple Myeloma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003eDenosumab (Xgeva)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eAmgen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eOsteolytic Bone Lesions of Multiple Myeloma, Hypercalcemia of Malignancy, Osteolytic Bone Metastases of Solid Tumors, Giant Cell Tumor of Bone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"4.081632653061225%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.367346938775512%\"\u003e\n \u003cp\u003ePanitumumab (Vectibix)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.26530612244898%\"\u003e\n \u003cp\u003eAmgen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.244897959183673%\"\u003e\n \u003cp\u003e2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.04081632653061%\"\u003e\n \u003cp\u003eColorectal Cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNSCLC: Non-small cell lung cancer; Classical HL: Classical Hodgkin Lymphoma; CRC: Colorectal cancer; HNSCC: Head and neck squamous cell carcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable- 3:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Characterization of cases including at the minimum single Neurological adverse event with mAbs in FAERS (period: date of first authorization to 30-June-2023).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"775\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"90.3225806451613%\" colspan=\"11\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eName of Drugs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePembrolizumab ICSRs (n=5331)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNivolumab ICSRs (n=8311)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAtezolizumab ICSRs (n=2677)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBevacizumab ICSRs (n=13441)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTrastuzumab ICSRs (n=7138)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRituximab ICSRs (n=23394\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIpilimumab ICSRs (n=3803)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDaratumumab ICSRs (n=2239)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDenosumab ICSRs (n=11095)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePanitumumab ICSRs (n=1593)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative count\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (Years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026le;25\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e22 (0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e74 (0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e7 (0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e182 (1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e16 \u0026nbsp;(0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e962 (4.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e26 (0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e12 (0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e26 (0.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e9 (0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1336 (1.69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e26\u0026ndash;50\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e367 (6.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e862 (10.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e214 (7.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1679 \u0026nbsp; \u0026nbsp; (12.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1546 \u0026nbsp; \u0026nbsp; (21.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3378 (14.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e515 (13.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e141 (6.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e394 (3.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e158 (9.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e9254 (11.71)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e51\u0026ndash;75\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2689 (50.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4456 (53.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1393 (52.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e6409 \u0026nbsp; \u0026nbsp; (47.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2816 \u0026nbsp; \u0026nbsp; (39.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e8584 (36.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2073 (54.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1043 (46.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4732 (42.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e926 (58.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e35121 (44.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026ge; 76\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e775 (14.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e1047 (12.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e310 (11.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1197 \u0026nbsp; \u0026nbsp; (8.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e270 \u0026nbsp;(3.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1435 (6.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e402 (10.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e308 (13.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e3286 (29.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e158 (9.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e9188 (11.63)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eUnknown\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e1478 (27.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e1872 (22.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e753 (28.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e3974 \u0026nbsp; \u0026nbsp; (29.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2490 (34.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e9035 (38.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e787 (20.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e735 (32.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e2657 (23.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e342 (21.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e24123 (30.53)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eMale (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2616 (49.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e2787 (33.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1315 (49.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e4946 \u0026nbsp; \u0026nbsp; (36.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e298 (4.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6253 (26.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2279 (59.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1044 (46.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e1319 (11.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e836 (52.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e23693 (29.98)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eFemale (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2433 (45.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4956 (59.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1088 (40.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e6678 \u0026nbsp; \u0026nbsp; (49.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6002 (84.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e12015 (51.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1251 (32.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e818 (36.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e9242 (83.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e590 (37.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e45073 (57.04)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eUnknown/Not Specified\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e282 (5.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e568 (6.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e274 (10.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1817 \u0026nbsp; \u0026nbsp; (13.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e838 (11.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e5126 (21.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e273 (7.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e377 (16.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e534 (4.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e167 (10.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e10256 (12.98)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase Seriousness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eSerious (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e4802 (90.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e7788 (93.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2596 (96.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e12885 \u0026nbsp; \u0026nbsp; (95.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6644 (93.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e22524 (96.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3576 (94.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2077 (92.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e3406 (30.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1514 (95.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e67812 (85.81)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNon-serious (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e529 (9.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e523 (6.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e81 (3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e556 \u0026nbsp;(4.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e494 (6.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e870 (3.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e227 (5.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e162 (7.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e7689 (69.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e79 (4.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11210 (14.19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase Priority\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eExpedited\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e4230 (79.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e7484 (90.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2563 (95.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e12353 \u0026nbsp; \u0026nbsp; (91.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6510 (91.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e22180 (94.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3435 (90.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1924 (85.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e5966 (53.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1146 (71.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e67791 (85.79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNon-Expedited\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e939 (17.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e671 (8.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e94 (3.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1012 \u0026nbsp; \u0026nbsp; (7.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e605 (8.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1106 (4.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e312 (8.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e288 (12.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4699 (42.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e446 (28.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e10172 (12.87)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eDirect (sender \u0026apos;Fda-Ctu\u0026apos;)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e162 (3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e156 (1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e20 (0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e76 \u0026nbsp;(0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e23 (0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e108 (0.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e56 (1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e27 (1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e430 (3.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1059 (1.34)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCo-suspect drugs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2640 (49.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e3835 (46.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e713 (26.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e3669 \u0026nbsp; \u0026nbsp; (27.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1508 (21.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6246 (26.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e818 (21.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e503 (22.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e9007 (81.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e603 (37.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e29542 (37.38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e1 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e1452 (27.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e3091 (37.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e885 (33.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e3523 \u0026nbsp; \u0026nbsp; (26.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1458 (20.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3321 (14.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2173 (57.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e372 (16.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e882 (7.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e186 (11.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e17343 (21.95)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e2 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e746 (13.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e721 (8.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e460 (17.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e2687 \u0026nbsp; \u0026nbsp; (19.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1442 (20.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2237 (9.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e397 (10.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e556 (24.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e422 (3.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e144 (9.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e9812 (12.42)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e3 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e210 (3.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e361 (4.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e368 (13.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1878 \u0026nbsp; \u0026nbsp; (13.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e961 (13.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1714 (7.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e250 (6.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e466 (20.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e208 (1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e396 (24.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e6812 (8.62)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e4 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e112 (2.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e127 (1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e100 (3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e802 \u0026nbsp;(5.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e639 (8.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2054 (8.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e76 (2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e125 (5.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e147 (1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e115 (7.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4297 (5.44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026ge;5 (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e171 (3.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e176 (2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e151 (5.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e882 \u0026nbsp;(6.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1130 (15.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e7822 (33.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e89 (2.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e217 (9.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e429 (3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e149 (9.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11216 (14.19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConcomitant drugs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eTaken\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2147 (40.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e3530 (42.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1457 (54.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e7243 \u0026nbsp; \u0026nbsp; (53.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3978 (55.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e12969 (55.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1639 (43.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1269 (56.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e5050 (45.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e855 (53.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e40137 (50.79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNot taken\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e3184 (59.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4781 (57.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1220 (45.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e6198 \u0026nbsp; \u0026nbsp; (46.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3160 (44.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e10425 (44.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2164 (56.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e970 (43.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e6045 (54.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e738 (46.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e38885 (49.21)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of reporter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eHealth professional (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e4139 (77.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e6339 (76.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2501 (93.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e11353 \u0026nbsp; \u0026nbsp; (84.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e5777 (80.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e19062 (81.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2998 (78.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1971 (88.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e5692 (51.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e116 (7.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e59948 (75.86)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNonhealth professional (Consumer) (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e1182 (22.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e1962 (23.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e174 (6.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1838 \u0026nbsp; \u0026nbsp; (13.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1273 (17.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e4102 (17.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e800 (21.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e264 (11.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e5370 (48.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1475 (92.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e18440 (23.34)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eUnknown (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e10 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e10 (0.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2 (0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e250 \u0026nbsp;(1.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e88 (1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e230 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e5 (0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e4 (0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e33 (0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2 (0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e634 (0.80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry where Event occurred\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eUS (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e2029 (38.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e2824 (33.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e399 (14.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e3971 \u0026nbsp; \u0026nbsp; (29.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1285 (18.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3811 (16.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1540 (40.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e677 (30.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e6457 (58.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e168 (10.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e23161 (23.31)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eNon-US (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e3075 (57.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e5429 (65.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1777 (66.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e8089 \u0026nbsp; \u0026nbsp; (60.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e5168 (72.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e17311 (74.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2229 (58.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1552 (69.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e4527 (40.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1395 (87.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e50552 (63.97)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eUnknown (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e227 (4.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e58 (0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e501 (18.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e1381 \u0026nbsp; \u0026nbsp; (10.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e685 (9.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2272 (9.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e34 (0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e10 (0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e111 (1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e30 (1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e5309 (6.72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFatal Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e942 (17.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e1555 (18.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e473 (17.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e2831 (21.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e790 (11.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2951 (12.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e602 (15.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e269 (12.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e685 (6.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e16 (1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11114 (14.06)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.67741935483871%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOthers outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\"\u003e\n \u003cp\u003e4389 (82.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e6756 (81.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e2204 (82.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806451612903226%\" valign=\"top\"\u003e\n \u003cp\u003e10610 (78.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e6348 (88.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e20443 (87.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e3201 (84.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1970 (87.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e10410 (93.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.516129032258064%\" valign=\"top\"\u003e\n \u003cp\u003e1577 (99.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.354838709677419%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e67908 (85.94)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable-4: Satisfactory values for all three statistical algorithms (PRR, IC\u003csub\u003e025\u003c/sub\u003e, and \u0026chi;2) for the safety reports of mAbs associated with PT of nervous system disorders (SOC) after disproportionality signal analysis extracted from FAERS safety database.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProducts (mAbs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent (SOC= \u0026apos;Nervous system disorders\u0026apos;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNcomb\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC\u003csub\u003e025\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eEncephalopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e151.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e55.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e46.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e61.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eCerebral Haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e120.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eNeurotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e316.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e266.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePosterior Reversible Encephalopathy Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e346.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eCognitive Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e32.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e522\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e493.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e1.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e738.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMemory Impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e198.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eParaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e1208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e766.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eSciatica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e228.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eIpilimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e236.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eTaste Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e227.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e5.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e811.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eDysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e58.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e720.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e236.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eNeurotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e348.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e4.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e296.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e110.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e6.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1039.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e322.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eSciatica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e310.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e1445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1013.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eLethargy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e141.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e239.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.291666666666664%\"\u003e\n \u003cp\u003eDysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e3.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e234.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePT: Preferred Term; SOC: System Organ Class, mAb: Monoclonal antibodies; Ncomb: Number of cases for specific drug-ADR combination; PRR: Proportional Relative Risk; IC\u003csub\u003e025\u003c/sub\u003e: Information Component; \u0026chi;2: Chi-square statistic; FAERS: FDA Adverse Event Reporting System.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable-5: Satisfactory values for 2 or more than two statistical algorithms (PRR, IC\u003csub\u003e025\u003c/sub\u003e, and \u0026chi;2) for the safety reports of mAbs associated with PT of nervous system disorders (SOC) after disproportionality signal analysis extracted from FAERS safety database.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003e\u003cstrong\u003eProducts (mAbs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent (SOC= \u0026apos;Nervous system disorders\u0026apos;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNcomb\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC\u003csub\u003e025\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNervous System Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e30.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eEncephalopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e151.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e55.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e46.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eAtezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e61.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebrovascular Accident\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e739\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e79.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eEncephalopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e198.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e61.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e458.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSeizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1043\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e361.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e120.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeurotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e316.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e266.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePosterior Reversible Encephalopathy Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e3.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e346.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTremor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e16.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSyncope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e30.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCognitive Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e32.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e522\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e493.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e1.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e738.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuralgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e48.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTremor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e6.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e19.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eDizziness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1416\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e167.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebrovascular Accident\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e719\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e185.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eBalance Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e91.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eHypoaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1066\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e373.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMemory Impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e198.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eParaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e766.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eDenosumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSciatica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e228.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eIpilimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e20.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eIpilimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e3.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e236.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSeizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e9.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e14.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSomnolence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e46.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e63.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTaste Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e227.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eNivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e5.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e811.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eDysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e58.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e720.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e236.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeurotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e4.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e348.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePanitumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e4.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e296.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSomnolence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e19.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTaste Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e39.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eCerebral Infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e110.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003ePembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMyasthenia Gravis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e6.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e1039.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eHypoaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e13.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSyncope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e30.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eDizziness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e2570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e94.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTremor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e36.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNervous System Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e30.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePosterior Reversible Encephalopathy Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e36.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eEncephalopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e190.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSomnolence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e140.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eLoss Of Consciousness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e856\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e121.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e5375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e1155.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eAmnesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e93.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e322.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSciatica\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e310.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuralgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e46.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eDizziness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e771\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e16.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSeizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e9.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eSyncope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e10.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eHypoaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e542\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e53.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTaste Disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e23.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eParaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e109.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eTremor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e99.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeurotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e66.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePeripheral Sensory Neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e1.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e64.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eNeuropathy Peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e1445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e1013.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eLethargy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e141.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003ePolyneuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e239.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.791666666666668%\"\u003e\n \u003cp\u003eTrastuzumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\"\u003e\n \u003cp\u003eDysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.375%\"\u003e\n \u003cp\u003e3.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e30.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcl","sideBox":"Learn more about [European Journal of Clinical Pharmacology](http://link.springer.com/journal/228)","snPcode":"228","submissionUrl":"https://submission.nature.com/new-submission/228/3","title":"European Journal of Clinical Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Monoclonal antibodies, neurological toxicity, FDA Adverse Event Reporting System Database (FAERS), signal detection, disproportionality signal analysis","lastPublishedDoi":"10.21203/rs.3.rs-4245237/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4245237/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMonoclonal antibodies (mAbs), are pivotal in treating various diseases including cancers and autoimmune disorders. Despite their therapeutic benefits, mAbs therapy has been associated with neurological toxicity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aimed to assess the incidence of neuronal toxicity associated with mAbs, utilizing data from the FDA Adverse Event Reporting System (FAERS) safety database. The study also sought to delineate the medical characteristics of the reported cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comprehensive analysis of neurological adverse events reported in the FAERS database was conducted, employing computational methodologies such as proportional relative risk (PRR), information component (IC\u003csub\u003e025\u003c/sub\u003e), and Chi-Square (χ2). Individual case safety reports (ICSRs) pertaining to neurological disorders linked to mAbs from the date of first global marketing authorization until June 30, 2023, were meticulously examined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe FAERS safety database contains 79,022 Individual Case Safety Reports (ICSRs) linking monoclonal antibodies (mAbs) to Nervous system disorders. Rituximab, Bevacizumab, Denosumab, Nivolumab, and Trastuzumab were frequently cited. Reported adverse events include headache, peripheral neuropathy, dizziness, and cerebrovascular accident. Most ICSRs (85.81%) were serious, mainly affecting females (57.04%) with a 14.09% fatality rate. Panitumumab, Atezolizumab, Bevacizumab, and Trastuzumab showed strong drug-event associations. Signal Disproportionate Reporting (SDR) analysis flagged myasthenia gravis, peripheral neuropathy, and neurotoxicity across multiple mAbs, suggesting potential signals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInterdisciplinary collaboration between oncologists and neurologists is crucial for safe mAb use. Our study enhances understanding of mAb neurological safety. Disproportionality signal analysis provides valuable evidence for risk mitigation.\u003c/p\u003e","manuscriptTitle":"Neuronal toxicity of Monoclonal antibodies (mAbs): An analysis of post marketing reports from FDA Adverse Event Reporting System (FAERS) safety database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-22 02:22:23","doi":"10.21203/rs.3.rs-4245237/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-21T13:20:40+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-21T12:51:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-07T16:04:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319261285662154541799195895868053956227","date":"2024-05-01T21:05:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"595ff388-4032-414d-b9c1-f2922c4d9015","date":"2024-04-18T08:48:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-18T05:06:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-15T06:01:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-15T06:01:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Clinical Pharmacology","date":"2024-04-10T05:31:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcl","sideBox":"Learn more about [European Journal of Clinical Pharmacology](http://link.springer.com/journal/228)","snPcode":"228","submissionUrl":"https://submission.nature.com/new-submission/228/3","title":"European Journal of Clinical Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a5d51ecb-a229-4f49-81f5-77c44d3dedc9","owner":[],"postedDate":"April 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T17:08:29+00:00","versionOfRecord":{"articleIdentity":"rs-4245237","link":"https://doi.org/10.1007/s00228-024-03727-0","journal":{"identity":"european-journal-of-clinical-pharmacology","isVorOnly":false,"title":"European Journal of Clinical Pharmacology"},"publishedOn":"2024-07-25 16:16:10","publishedOnDateReadable":"July 25th, 2024"},"versionCreatedAt":"2024-04-22 02:22:23","video":"","vorDoi":"10.1007/s00228-024-03727-0","vorDoiUrl":"https://doi.org/10.1007/s00228-024-03727-0","workflowStages":[]},"version":"v1","identity":"rs-4245237","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4245237","identity":"rs-4245237","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}