Analysis Of Safety Data Research Articles

Aggregate Safety Assessment Planning for the Drug Development Life-Cycle.

The Program Safety Analysis Plan (PSAP) was proposed previously as a tool to proactively plan for integrated analyses of product safety data. Building on the PSAP and taking into consideration the evolving regulatory landscape, the Drug Information Association-American Statistical Association (DIA-ASA) Interdisciplinary Safety Evaluation scientific working group herein proposes the Aggregate Safety Assessment Plan (ASAP) process. The ASAP evolves over a product's life-cycle and promotes interdisciplinary, systematic safety planning as well as ongoing data review and characterization of the emerging product safety profile. Objectives include alignment on the safety topics of interest, identification of safety knowledge gaps, planning for aggregate safety evaluation of the clinical trial data and preparing for safety communications. The ASAP seeks to tailor the analyses for a drug development program while standardizing the analyses across studies within the program. The document is intended to be modular and flexible in nature, depending on the program complexity, phase of development and existing sponsor processes. Implementation of the ASAP process will facilitate early safety signal detection, improve characterization of product risks, harmonize safety messaging, and inform program decision-making.

First Month of COVID-19 Vaccine Safety Monitoring - United States, December 14, 2020-January 13, 2021.

Two coronavirus disease 2019 (COVID-19) vaccines are currently authorized for use in the United States. The Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine on December 11, 2020, and for the Moderna COVID-19 vaccine on December 18, 2020; each is administered as a 2-dose series. The Advisory Committee on Immunization Practices issued interim recommendations for Pfizer-BioNTech and Moderna COVID-19 vaccines on December 12, 2020 (1), and December 19, 2020 (2), respectively; initial doses were recommended for health care personnel and long-term care facility (LTCF) residents (3). Safety monitoring for these vaccines has been the most intense and comprehensive in U.S. history, using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, and v-safe,* an active surveillance system, during the initial implementation phases of the COVID-19 national vaccination program (4). CDC conducted descriptive analyses of safety data from the first month of vaccination (December 14, 2020-January 13, 2021). During this period, 13,794,904 vaccine doses were administered, and VAERS received and processed† 6,994 reports of adverse events after vaccination, including 6,354 (90.8%) that were classified as nonserious and 640 (9.2%) as serious.§ The symptoms most frequently reported to VAERS were headache (22.4%), fatigue (16.5%), and dizziness (16.5%). A total of 113 deaths were reported to VAERS, including 78 (65%) among LTCF residents; available information from death certificates, autopsy reports, medical records, and clinical descriptions from VAERS reports and health care providers did not suggest any causal relationship between COVID-19 vaccination and death. Rare cases of anaphylaxis after receipt of both vaccines were reported (4.5 reported cases per million doses administered). Among persons who received Pfizer-BioNTech vaccine, reactions reported to the v-safe system were more frequent after receipt of the second dose than after the first. The initial postauthorization safety profiles of the two COVID-19 vaccines in current use did not indicate evidence of unexpected serious adverse events. These data provide reassurance and helpful information regarding what health care providers and vaccine recipients might expect after vaccination.

Abstract OT-13-06: Solti-1503 PROMETEO: Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer

Abstract Background Residual disease (RD) after standard neoadjuvant chemotherapy (NAC) is composed of drug resistant cells and associates with increased risk of relapse, especially in triple negative, HER2-positive, and highly proliferative Luminal tumors. Immunotherapy combinations can induce of specific anti-tumor immune responses, such as those mediated by T-cells, and which might represent an additional strategy for the control or elimination of residual tumor cells. Preliminary results in melanoma showed that the combination of T-VEC with an anti PD-L1 or anti CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of RD after neoadjuvant chemotherapy (NAC) in early BC patients remains an unmet medical need. We hypothesize that combining T-VEC with Atezolizumab may offer clinical benefit in the preoperative setting for early breast cancer (BC) patients with intermediate to high risk of recurrence who present RD after standard NAC. Methods SOLTI-1503 PROMETEO is an open-label, multicenter trial of T-VEC + Atezolizumab in patients with RD after completing standard NAC. Thirty patients with triple negative BC (TNBC) or Luminal B-like/HER2- will be included. RD must be confirmed by core-biopsy and have a diameter ≥ 15 mm measured by magnetic resonance imaging. Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally in week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for 4 infusions, beginning in week 4. BC surgery will be carried out 1 to 3 weeks after completion of treatment. A protocol amendment was approved, the steering committee of the study decided to change the primary objective of the trial to a more clinical endpoint that is to evaluate the efficacy by the rate of RCB class 0/1 at surgery. Secondary endpoints include rate of pCR, ORR, safety and the increase of mean expression of a gene signature tracking activated CD8 T-cells. The first safety analysis was performed in October 2019. Independent safety date review board considered the trial safe and supported its continuation. To date, 8 patients have been included at 4 sites in Spain. Second safety and efficacy data analysis is planned after 10 patients have completed treatment. If a rate of PD higher than 50% is observed in the first 10 patients, then the trial will be permanently stopped. We expect to achieve 10 patients in July 2020. We thank AMGEN for their provision of Talimogene Laherparepvec and their financial contribution to this clinical study. We thank ROCHE for their provision of Atezolizumab and their financial contribution to this clinical study. Clinical trial identification: NCT03802604 Citation Format: Tomás Pascual, Juan M Cejalvo, Mafalda Oliveira, Maria Vidal, Estela Vega, Sergi Ganau, Ana Julve, Esther Zamora, Ignacio Miranda, Ana Delgado, Begoña Bermejo, Luis de la Cruz-Merino, Manel Juan, Juan M Ferrero-Cafiero, Jordi Canes, Xavier González-Farré, Patricia Villagrasa, Aleix Prat. Solti-1503 PROMETEO: Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-06.

Construct Food Safety Traceability System for People’s Health Under the Internet of Things and Big Data

In the context of epidemic prevention and control, food safety monitoring, data analysis and food safety traceability have become more important. At the same time, the most important reason for food safety issues is incomplete, opaque, and asymmetric information. The most fundamental way to solve these problems is to do a good job of traceability, and establish a reasonable and reliable food safety traceability system. The traceability system is currently an important means to ensure food quality and safety and solve the crisis of trust between consumers and the market. Research on food safety traceability systems based on big data, artificial intelligence and the Internet of Things provides ideas and methods to solve the problems of low credibility and difficult data storage in the application of traditional traceability systems. Therefore, this research takes rice as an example and proposes a food safety traceability system based on RFID two-dimensional code technology and big data storage technology in the Internet of Things. This article applies RFID technology to the entire system by analyzing the requirements of the system, designing the system database and database tables, encoding the two-dimensional code and generating the design for information entry. Using RFID radio frequency technology and the data storage function in big data to obtain information in the food production process. Finally, the whole process of food production information can be traced through the design of dynamic query platform and mobile terminal. In this research, the food safety traceability system based on big data and the Internet of Things guarantees the integrity, reliability and safety of traceability information from a technical level. This is an effective solution for enhancing the credibility of traceability information, ensuring the integrity of information, and optimizing the data storage structure.

Research and development of comprehensive safety management system for super-tall buildings in Shanghai

In order to meet the requirements of comprehensive safety management of super-tall buildings, a set of integrated safety management system is developed, which can be popularized and demonstrated, including three subsystems of structure, enclosure and firefighting. Interfaces are reserved for water supply and drainage, facilities and equipment, strong and weak electricity and other building safety management subsystems, which can realize the functions of comprehensive safety assessment, safety early warning, Internet of things safety monitoring and data analysis of super-tall buildings. Through the demonstration application in Shanghai Center, it is eventually proved that the system is feasible and effective.

15261 Lack of tuberculosis reactivation in 12,319 patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis treated with secukinumab: An ad hoc analysis of pooled safety data from 28 clinical trials

Introduction: TNFα inhibitors (TNFi) may increase the risk of tuberculosis (TB) and latent TB infection (LTBI) reactivation; however, data on the effects of newer biologic agents and TB is limited. This pooled safety analysis of patients treated with secukinumab, a human monoclonal antibody neutralizing IL-17A, reports long-term observed incidence rates of TB/LTBI in psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

First Nation-Wide Analysis of Food Safety and Acceptability Data in Lebanon.

The challenges to food safety in Lebanon are numerous and have coalesced to pose a serious public health concern. This is evident in well-documented food poisoning outbreaks and adulteration cases. In response, the Lebanese government initiated an unprecedented food safety campaign (2015–2017) that aimed to test food samples that were randomly collected from foodservices and industries across the country. The data were made available publicly, but they were never analyzed to prioritize and determine high risk foods and most prevalent contaminants nationally or across governorates. To answer these questions, we performed an in-depth statistical analysis of the data, which included 11,625 individual food samples. Our analysis showed that water (55% of tested water samples), spices (49.3%), red meat (34.4%), poultry (30.9%) and dairy (28.3%) were the main foods associated with the highest rejection rates. The most common biological contaminants detected in rejected foods were sulfate-reducing bacteria (34.7%), Escherichia coli (32.1%), coliforms (19.6%), Staphylococcus aureus (12.8%), and Salmonella (11.6%). We conclude that Lebanon needs rigorous and sustainable programs to monitor the quality and safety of foods. Given the lack of resources, we recommend putting emphasis on extensive outreach programs that aim at enhancing food safety knowledge from farm to fork.

Efficacy and Safety of Mesenchymal Stem Cells in Treatment of Complex Perianal Fistulas: A Meta-Analysis.

Complex perianal fistula is a highly debilitating and difficult to treat condition. Local mesenchymal stem cell (MSC) therapy for perianal fistula has shown considerable promise but still remains controversial. Therefore, we performed the meta-analysis to evaluate the efficacy and safety of local MSC therapy for complex perianal fistula. PubMed and Embase databases were searched for published randomized clinical trials (RCTs) that reported local MSC therapy for complex perianal fistulas. The effectiveness and safety data analysis was conducted using RevMan5.3. Subgroup analyses were performed based on the characteristics of the studies. Seven RCTs with 730 participants were included. Local MSC treatment showed significantly higher healing rate (HR) of perianal fistulas compared to control (odds ratio (OR) = 2.03; 95% confidence interval (CI) 1.50, 2.74; P < 0.00001). MSCs combined with fibrin glue therapy can improve the HR compared with fibrin glue alone (OR = 3.27; 95% CI 1.15, 9.28; P = 0.03). Subgroup analyses showed that local therapy can improve the HR in patients with perianal fistulas associated with Crohn's disease (CD) (OR = 2.05; 95% CI 1.41, 3.00; P = 0.0002) and cryptoglandular origin (no-Crohn) (OR = 2.98; 95% CI 0.86, 10.29; P = 0.08). The pooled OR for studies that combined reepithelialization of the external opening with pelvic magnetic resonance imaging (MRI) to evaluate the healing of fistulas was 1.77 (95% CI 1.28, 2.45; P = 0.0006). The pooled OR for studies where fistula healing was defined as complete reepithelialization of external openings was 5.92 (95% CI 1.34, 26.15; P = 0.02). Both autologous MSCs (OR = 3.19; 95% CI 1.05, 9.65; P = 0.04) and allogeneic MSCs (OR = 1.97; 95% CI 1.34, 2.91; P = 0.0006) can obtain higher HR for perianal fistula compared with control. The adipose-derived MSC group can obtain higher HR than the control group (OR = 2.29; 95% CI 1.38, 3.79; P = 0.001). There were no significant differences in adverse events (AEs) (OR = 1.06; 95% CI 0.71, 1.59; P = 0.77). None of the adverse events was judged to be related to MSCs. Our study supported that local MSC therapy alone or combined with fibrin glue is safe and efficacious for complex perianal fistula. In the future, more RCTs are needed to confirm this conclusion.

Dreamm-5 Platform Trial: Belantamab Mafodotin (Belamaf) in Combination with Four Different Novel Agents in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Dreamm-5 Platform Trial: Belantamab Mafodotin (Belamaf) in Combination with Four Different Novel Agents in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Long-Term Safety Profile of the Oral Spleen Tyrosine Kinase Inhibitor Fostamatinib in Immune Thrombocytopenia (ITP) and Other Diseases

Introduction: Fostamatinib is an oral, potent inhibitor of spleen tyrosine kinase (SYK) with proven efficacy and a manageable safety profile for the treatment of ITP. SYK is situated in an intracellular signaling pathway upstream of Bruton's tyrosine kinase (BTK). Long-term safety data on fostamatinib at various dosing regimens (up to 150 mg BID) has been collected in &amp;gt;4000 patients with ITP, rheumatoid arthritis (RA), and other autoimmune, allergic and neoplastic disorders. The safety and tolerability of fostamatinib were consistent across different patient populations (apart from disease specific events). We present a summary analysis of the fostamatinib safety data from the ITP and RA studies. Methods: Fostamatinib safety data from 2 randomized, double-blind, placebo-controlled, phase 3 studies and the long-term, open-label, extension (OLE) study in ITP were pooled and are based on a starting dose of 200 mg/day, which was increased to 300 mg/day after 4 weeks in 88% of patients. Fostamatinib safety data from 13 phase 2/3 studies in RA were pooled and are based on a dosing regimen of 100-150 mg/day (n=1232) or 200-300 mg/day (n=2205). Results: The pooled data set for ITP included 146 patients; 60% were female, and the median age was 53 years (range 20-88). The mean duration of fostamatinib treatment was 19 months (range &amp;lt;1-62 months), representing 229 patient exposure years. Adverse events (AEs) were reported in 87% of patients, and 63% were mild to moderate. Serious AEs were reported in 31% of patients. The incidence of diarrhea, hypertension, alanine aminotransferase increase (ALT), and aspartate aminotransferase (AST) increase was evaluated in 58 patients who received fostamatinib for ≥1 year. This enabled a comparison of the incidence of these AEs in quartiles over the first year to assess the cumulative effects of fostamatinib. The AEs were reported with decreasing frequency during the second, third, and fourth quarters of fostamatinib treatment compared with the first quarter of the initial year of treatment in the 58 patients (see Figure 1). In the same 58 patients, the use of rescue therapy decreased while median platelet counts increased each quarter of the first year. The pooled data set for RA included 3437 patients who received fostamatinib; 83% were female, and the median age was 54 (range 18 -87). The mean duration of treatment was 18 months (range &amp;lt;1-81) representing 5134 patient exposure years. AEs were reported in 86% of RA patients and were mild to moderate in 73% of RA patients. Serious AEs occurred in 14%. In the placebo-controlled RA studies, 2414 patients received fostamatinib with 823 patient exposure years and 1169 received placebo with 367 patient exposure years. Despite a two-fold (125%) increase in exposure with fostamatinib vs placebo (823 vs 367 patient exposure years), there was only a 26% increase in AEs with fostamatinib vs placebo (68% vs 54%). The most common events in the ITP and RA studies were diarrhea (36% and 24%), hypertension (22% and 19%) and nausea (19% and 8%), apart from disease-related AEs. Epistaxis (19% and 0.5%), petechiae (15% and 0.3%), contusion (12% and 2%), and fatigue (10% and 2%) are associated with ITP and were uncommon in the RA population. Rheumatoid arthritis was reported as an AE in 9% of patients with RA and in none with ITP. Some AEs may be dose-related, and one-third of the RA patients were on lower dosages (100-150 mg/day) than were generally given in the ITP trials (200-300 mg/day). Conclusions: Fostamatinib has been evaluated in &amp;gt;4000 patients across different disease populations. Fostamatinib has a consistent and manageable safety profile. No new safety signals and no cumulative toxicity were observed with up to 81 months (6.8 years) of continuous treatment. Figure 1 Disclosures Tong: Rigel: Current Employment, Current equity holder in publicly-traded company. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Datangel:Rigel: Current Employment, Current equity holder in publicly-traded company. Masuda:Rigel: Current Employment, Current equity holder in publicly-traded company.

Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation and Maintenance in Subjects with High Risk Smoldering Multiple Myeloma (SMM): Initial Analysis of Safety Data

Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation and Maintenance in Subjects with High Risk Smoldering Multiple Myeloma (SMM): Initial Analysis of Safety Data

Pooled Analysis of Safety Data from Clinical Trials of Orelabrutinib Monotherapy in Hematologic Malignancies

Background: Bruton tyrosine kinase (BTK) is one of the key kinases implicated in the pathogenesis of multiple B cell malignancies. Orelabrutinib is a novel, highly selective and potent irreversible BTK inhibitor with minimal activities against other kinases (ITK, EGFR, ERBB2, etc.). As thus orelabrutinib may avoid off-target related adverse events and shall have improved safety profiles comparing to other BTK inhibitors. Here we present the safety profile of orelabrutinib analyzed based on data from 5 ongoing clinical studies in B cell malignancies (Table 1). Methods: Safety data of 266 patients (pts) from 5 ongoing orelabrutinib monotherapy studies were pooled and analyzed. All pts have been treated with at least one dose of oral orelabrutinib at ≥150 mg daily. The analysis includes the frequency and severity of adverse events (AEs), AEs of special interest, and AEs leading to treatment discontinuation or dose modifications. Results: Safety data were pooled from 266 pts with median age of 60 years (range 35.0-79.0, 69.2% males). The median duration of exposure was 11.0 months (range 0.2-22.0). The most common (occurring in ≥15% of pts) AEs were neutropenia (28.6%), thrombocytopenia (25.9%), Upper respiratory tract infection (24.4%), leukopenia (18.0%), anemia (16.2%) and rash (15.8%). Treatment related serious AEs (SAEs) were reported in 14.7% pts. The most common treatment related SAEs included thrombocytopenia (3.0%), lung infection (3.0%), pneumonitis (1.9%), anemia (1.1%) and lymphadentis (0.8%), The safety profiles were comparable in pts with various subtypes of B cell malignancies. It's noted that orelabrutinib has much less frequency of BTK off-target related adverse events, such as atrial fibrillation, diarrhea, major hemorrhage etc. Among all 266 pts, only one patient was reported with one episode of transient grade 1 atrial fibrillation, and no grade ≥3 atrial fibrillation was observed. Diarrhea of any grade was 7.1% and only one case (0.4%) was reported as grade 3. The major hemorrhage, defined as serious or ≥ G3 bleeding of any site, or central nervous system bleeding of any grade, was rarely observed; as only one case of cerebral hemorrhage, in 65-year-old male patient with more than 10 years hypertension was reported; the other three cases were subcutaneous hemorrhage, vitreous hemorrhage and vitreous hemorrhage/retinal hemorrhage. The later 2 cases of vitreous hemorrhage and/or retinal hemorrhage were resulted from posterior vitreous detachment and macular degeneration and both events were assessed as unlikely related to the treatment. Among 266 pts, the second primary malignancies were reported in only one pt with r/r MCL during orelabrutinib treatment. Grade ≥3 infection occurred in 41 pts (15.4%); most common infections were upper respiratory tract infection and lung infection. Most of the AEs were occurred during the early treatment, the frequency of the new event occurrence was significantly decreased during the later cycles. Dose reductions due to AEs occurred in 15 pts (5.6%), and treatment discontinuation due to AEs in 5.3% of pts with 2.3% related to orelabrutinib. Conclusions: Orelabrutinib shows excellent safety profiles and tolerability across various B-cell malignancies in long-term treatment. These data suggested orelabrutinib as a favorable treatment choice including the combinational therapy for B-cell malignancies. . Disclosures Zhu: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Xu:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment.

Guidance for vaccine safety data collection, presentation and analysis (SO1-D2.7)

Guidance for vaccine safety data collection, presentation and analysis (SO1-D2.7)

The application of extreme value theory to pharmacometrics.

Clinical trials are often analyzed by examining the means, e.g., what is the mean treatment effect or what is the mean treatment difference, but there are times when analysis of the maximums (or minimums) are of interest. For instance, what is the highest heart rate that could be observed or what the smallesttreatment effect that could be expected? While inference on the means is based on the central limit theorem, the corresponding theorem for maximums or minimums is the Fisher-Tippett theorem, also called the extreme value theorem (EVT). This manuscript will introduce EVT to pharmacometricians, particularly block maxima analysis and peak over threshold analysis, and provide examples for how it can be applied to pharmacometric data, particularly the analysis of pharmacokinetics and ECG safety data, like QTcF intervals.

Long-term safety data from the cladribine tablets clinical development program in multiple sclerosis

BackgroundLong-term safety data are of particular interest for any newly approved treatment in multiple sclerosis such as cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg), which is approved in Europe and the USA. Here we provide the final report on the integrated analysis of the safety profile of cladribine tablets 3.5 mg/kg from the clinical development program, including final data from the PREMIERE registry. MethodsSafety data for cladribine tablets 3.5 mg/kg from three previously reported Phase III studies (CLARITY, CLARITY Extension and ORACLE-MS), as well as the prospective, observational PREMIERE registry (which ran from November 2009 to October 2018; consisting of patients who had participated in at least one of the Phase III trials) were combined to provide the Monotherapy Oral cohort. Serious adverse events (SAEs) and predefined SAEs of special interest were recorded. Observation-adjusted incidence rates per 100 patient-years (Adj-AE per 100 PY) were used to assess adverse events (AEs). Standardized incidence ratios for malignancies were calculated in relation to a matched GLOBOCAN reference population, and risk differences (cladribine tablets versus placebo) were estimated. ResultsThe Monotherapy Oral cohort comprised 923 patients who received cladribine tablets 3.5 mg/kg and 641 patients who received placebo. Overall, the reported number of SAEs was higher in the cladribine tablets 3.5 mg/kg group (133/923 [14.4%] patients with at least 1 SAE), versus the placebo group (68/641 [10.6%] patients with at least 1 SAE). Four patients in the cladribine tablets 3.5 mg/kg group had lymphopenia classified as a serious event (resulting in an Adj-AE of 0.10 per 100 PY) and 2 patients had serious herpes zoster (resulting in an Adj-AE of 0.05 per 100 PY). There were no cases in the corresponding placebo groups. There was no difference between the cladribine tablets 3.5 mg/kg group and placebo in the overall incidence of infections. However herpetic infection AEs occurred more frequently in the cladribine tablets 3.5 mg/kg group (driven primarily by herpes zoster, followed by oral herpes and herpes simplex). Overall, there was a numerical imbalance in malignancy incidence between cladribine tablets 3.5 mg/kg and placebo, with an Adj-AE of 0.26 and 0.12 per 100 PY, respectively; however the difference was not statistically significant. The rate of malignancies observed with cladribine tablets 3.5 mg/kg in the final integrated safety analysis was not different from the expected rate in the matched GLOBOCAN reference population (standardized incidence ratio, 0.88; 95% CI, 0.44–1.69). ConclusionAdditional patient-years of observation do not significantly alter the conclusions of earlier interim analyses, and no new major safety findings were identified in this consolidated analysis of safety data of cladribine tablets 3.5 mg/kg monotherapy in patients with relapsing-remitting multiple sclerosis.

Application Case of Safety Stock Policy based on Demand Forecast Data Analysis

The fourth industrial revolution encourages manufacturing industry to pursue a new paradigm shift to meet customers' diverse demands by managing the production process efficiently. However, it is not easy to manage efficiently a variety of tasks of all the processes including materials management, production management, process control, sales management, and inventory management. Especially, to set up an efficient production schedule and maintain appropriate inventory is crucial for tailored response to customers' needs. This paper deals with the optimized inventory policy in a steel company that produces granule products under supply contracts of three targeted on-time delivery rates. For efficient inventory management, products are classified into three groups A, B and C, and three differentiated production cycles and safety factors are assumed for the targeted on-time delivery rates of the groups. To derive the optimized inventory policy, we experimented eight cases of combined safety stock and data analysis methods in terms of key performance metrics such as mean inventory level and sold-out rate. Through simulation experiments based on real data we find that the proposed optimized inventory policy reduces inventory level by about 9%, and increases surplus production capacity rate, which is usually used for the production of products in Group C, from 43.4% to 46.3%, compared with the existing inventory policy.

Overlap between adverse events (AEs) and serious adverse events (SAEs): a case study of a phase III cancer clinical trial

BackgroundSafety data is required to be collected in all clinical trials and can be separated into two types of data, adverse events and serious adverse events. Often, these types of safety data are collected as two discrete data sets, where adverse events that also meet the criteria for seriousness should be reported in both datasets. Safety analyses are often conducted using only the adverse event dataset, which should feature all safety events reported. We investigated whether the reporting of safety in both datasets was systematically followed and explored the impact of this on safety analyses in ICON8, an ovarian cancer clinical trial.MethodsText searches of serious adverse event data identified events that could potentially match the data reported in the adverse event dataset (looking at pre-specified AE terms only). These serious adverse events were then mapped to adverse event data according to predefined criteria: (a) event term matches, (b) date of onset and date of assessment within 30 days of each other, (c) date of assessment lies between date of onset and date of resolution and (d) events confirmed to occur in the same chemotherapy cycle. A combined dataset of all unique safety events (whether originally reported in the adverse event or serious adverse event dataset) was created and safety analyses re-performed.Results51,019 adverse events were reported in ICON8, of which 42,410 were included in the mapping exercise. One thousand five hundred six serious adverse event elements were reported, of which 668 were included in the mapping exercise. Sixty-one percent of serious adverse event elements was matched to an already-reported adverse event. Supplementing these additional safety events and re-performing safety analyses increased the proportion of patients with at least one grade 3 or worse safety events in all arms from 42 to 47% in the control arm and 61 to 65% and 52 to 59% in the research arms. The difference in proportions of grade 3 or worse event in the research arms compared to the control arm changed by 18% (95% confidence interval [CI] 12 to 24%) and 12% (95% CI 6 to 18%), respectively.ConclusionsThere was low agreement in mapping serious adverse events to already reported adverse events, with nearly 40% of serious adverse events included in the mapping exercise not mapped to an already reported adverse event. Any analyses of safety data that use only adverse event datasets or do not clearly account for serious adverse event data will likely be missing important safety information. Reporting standards should make clear which datasets were used for analyses.

Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data

ObjectivesTofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an...

Using on-board video data for safety analysis – An analysis of right hook crashes involving large buses at signalized intersections

Bus right hook (BRH) crashes at intersections are one of the most common types of crashes for bus carriers, which accounted for as high as 16% of fatal and injury crashes involving large buses at intersections in Taiwan. A BRH crash occurs when a bus and another vehicle traveling in the same direction head into an intersection, but the bus driver makes a right turn across the path of the through-moving vehicle, and both vehicles collide. This study responds to the research needs to identity factors associated with BRH crashes by utilizing in-vehicle data recorder (IVDR) data. A four step analysis procedure was developed, including (1) video data coding, (2) crash sequence analysis to identify crash contributing factors, (3) a case-control study to examine the relationship between the crash contributing factors and crash occurrence, and (4) modeling crash risk in terms of the crash contributing factors to better understand the crash generating process. This study first identified the existence of driver unattended time as the time between when the driver last checked the right back mirror to finally steering for a right turn, indicating the time period wherein the driver did not track the through vehicle on the right side using the right back mirror. It was found that BRH crashes could be attributed to the concurrence of unattended time and the speed difference between the bus and through vehicle. Several recommendations are discussed based on the results to further develop countermeasures to reduce this type of crash.

Recognition of the Name of Quality Inspection Institutions Based on CRF and Rules

In recent years, the case of injuries, deaths and property losses caused by product quality and safety issues occurred frequently. The analysis and processing of product quality and safety data can provide data support for government departments in decision-making, which is significant for improving product quality and safety in general. Institution name recognition is an important link in the analysis and processing of quality inspection data. A recognition method which combined CRF and rules for the name of quality inspection institution is put forward in this paper. Firstly, summarizing the rules and features of the name of quality inspection institution by the analysis of the composition characteristics, and then the entity recognition model based on statistics and rules is constructed in combination with CRF. The experimental results show that the method proposed this paper has high accuracy, recall rate and F value for the quality inspection institution names of different scales.