Perspectives on trace chemical safety and chemophobia: risk communication and risk management

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia, i.e., the fear of chemicals. Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.     

我国药品安全风险交流现状研究

目的探讨我国药品风险交流的现状,促进药品风险交流工作的开展,为下一步制定药品安全风险交流工作指南提供依据。方法通过查阅文献,检索我国相关法律法规,浏览官方网站等方式,分析我国目前药品风险交流的主要方式与途径,揭示目前存在的问题并提出完善我国药品安全信息交流的建议。结果与结论我国的药品风险沟通制度尚不完善,缺乏与之相配套的法律、法规。建议制定我国药品风险交流指南性文件;积极开展主管部门与医疗机构之间的交流研究;建立药品安全信息交流咨询委员会;实行多种形式的风险信息发布等。     

Regulatory assessment and risk management of chemical mixtures: challenges and ways forward

Abstract

This paper summarizes current challenges, the potential use of novel scientific methodologies, and ways forward in the risk assessment and risk management of mixtures. Generally, methodologies to address mixtures have been agreed; however, there are still several data and methodological gaps to be addressed. New approach methodologies can support the filling of knowledge gaps on the toxicity and mode(s) of action of individual chemicals. (Bio)Monitoring, modeling, and better data sharing will support the derivation of more realistic co-exposure scenarios. As knowledge and data gaps often hamper an in-depth assessment of specific chemical mixtures, the option of taking account of possible mixture effects in single substance risk assessments is briefly discussed. To allow risk managers to take informed decisions, transparent documentation of assumptions and related uncertainties is recommended indicating the potential impact on the assessment. Considering the large number of possible combinations of chemicals in mixtures, prioritization is needed, so that actions first address mixtures of highest concern and chemicals that drive the mixture risk. As chemicals with different applications and regulated separately might lead to similar toxicological effects, it is important to consider chemical mixtures across legislative sectors.     

关于改进我国药品风险沟通的研究

文中通过研究国际药品注册协调委员会(ICH)的质量风险管理Q9(Quality Risk Management)中的风险沟通内涵和美国食品药品监督管理局(FDA)发布的系列风险沟通指南,分析了FDA风险沟通的特点,指出了我国药品风险沟通中存在的问题。借鉴美国的经验,就我国药品风险沟通的建设从科学性、针对性、互动性和时效性方面提出了建议。     

护理风险管理在同单元多学科病区安全管理中的应用

目的：探讨护理风险管理在同单元多学科病区安全管理中的应用效果。方法成立风险管理小组,评估同单元多学科病区护理风险点,提出风险管理的措施。结果护理人员提高了风险防范意识,病区投诉率和护理不良事件发生率降低,患者对护理工作满意度提高。结论同单元多学科病区实施护理风险管理可有效提高护理人员的风险防御能力,降低或避免护理不良事件的发生,确保患者的护理安全,提高患者满意度,具有重要作用。     

国内外对加替沙星安全性处置情况的比较与分析

目的通过比较分析国内外对加替沙星安全性问题的处置情况，了解我国药品安全性管理中存在的问题。方法通过期刊数据库查阅国内外有关加替沙星引起血糖异常的药品不良反应报道，比较国内外相关机构对此所做出的反应和所采取的措施誊结果国内外对加替沙星安全性信息的收集、反应的灵敏性、所采取措施的有效性等方面存在差距。结论我国应进一步加强对药品安全性监测系统的建设，健全与完善相关的制度与法规，最大限度地保障公众的用药安全。     

ICH和欧盟药品风险管理指南简介

风险评估贯穿于整个药品生命周期,风险管理的目的 在于不断提高药品使用环节的安全性,通过对药物安全性信号和风险控制手段的有效研究,去合理规避一些不当用药行为.随着我国注册技术新要求的出台,开展药品风险管理的方法 学研究以及制定和提交风险控制计划将不会遥远.通过对国外相关指南的介绍,期望对这项工作带来一些启发.     

中药安全性认识和中药新药研发的风险管理策略

一直以来中药安全性是监管的热点和难点问题。为了提升对中药安全性的全面认识,本文从立足于临床应用的角度,对毒药和毒性的起源、沿革以及安全性认识等方面进行梳理和总结,分析中药安全性风险管理存在的关键技术问题,如基础研究薄弱、安全性风险防控措施研究不足、安全性研究成果对临床应用的指导性有限等,并提出探索建立中药安全性风险管理流程、充分挖掘利用有毒中药的疗效特点及加强对已知中药安全性风险的警示等有针对性的风险管理建议,以期为促进中药安全性风险管理提供借鉴。     

Research strategies for safety evaluation of nanomaterials, part VII: evaluating consumer exposure to nanoscale materials.

Considerable media attention has recently been given to novel applications for products that contain nanoscale materials. These products could have utility in several industries that market consumer products, including textiles, sporting equipment, cosmetics, consumer electronics, and household cleaners. Some of the purported benefits of these products include improved performance, convenience, lower cost, as well as other desirable features, when compared to the conventional products that do not contain nanoscale materials. Although there are numerous likely consumer advantages from products containing nanoscale materials, there is very little information available regarding consumer exposure to the nanoscale materials in these products or any associated risks from these exposures. This paper seeks to review a limited subset of products that contain nanoscale materials, assess the available data for evaluating the consumer exposures and potential hazards associated with these products, and discuss the capacity of U.S. regulatory agencies to address the potential risks associated with these products.     

Factors influencing the implementation of medicine risk communications by healthcare professionals in clinical practice: A systematic review

BackgroundRegulatory medicines risk communications aim to prevent patient harm through the dissemination of safety information to healthcare professionals (HCPs), patients, and the public. Evidence suggests that in addition to implementing the required changes, HCPs also respond to these communications through unintended and unwarranted actions and behaviours such as stopping medicine courses unnecessarily, and blanket actions spilling over to unintended patients' populations. Misunderstanding and mis-implementation of medicines risk communications could jeopardise patients’ safety and clinical outcomes. Therefore, it is important to understand the determinants that affect HCPs responses to medicines risk communications. This systematic review aims to identify the factors that affect the implementation of risk communications by healthcare professionals.MethodsFifteen databases, including EMBASE, PubMed, Scopus, Web of science, CINAHL PLUS were searched in April–May 2018, and the search was updated again in June 2021 to identify studies reporting on factors influencing HCPs' uptake of medicine risk alerts. We used keywords such as risk communication, safety update, and safety regulation. Studies were excluded if they did not involve pharmacovigilance or patient safety alerts; or if they only focused on measuring HCPs' practice after alerts; or evaluating the effectiveness of risk minimisation measures without reporting on factors affecting HCPs’ actions. Studies relating to occupational hazards, case reports, interventional studies, and studies not involving HCPs were also excluded. The Mixed Method Appraisal Tool (MMAT) was used to assess the quality of the included studies. A Narrative synthesis approach was undertaken using thematic analysis and concept mapping, followed by a critical reflection of the synthesis.ResultsTwenty-eight studies met our criteria and were included in the synthesis. We identified four themes summarising the factors influencing HCPs’ implementation of risk communications. These include HCPs: knowledge of medicine alerts; perceptions of alerts; attitudes, and concerns regarding medicine alerts; and the self-reported impact of these alerts. Our concept mapping exercise identified key interactions between different stakeholders, and these interactions determine HCPs' implementation of medicine risk communications. These stakeholders comprise of alert developers, including the sources and senders of safety information, and the receivers of safety information including health care institutions, HCPs, patients and their carers.ConclusionsHealthcare professionals are crucial to translating risk communication messages into clinical practice. However, if they have inadequate information about the content of the alert, and have inaccurate perceptions about the alert, they may not implement the required clinical changes as intended. Communication of medicine risk alerts does not always translate into improved patient care, due to a complex interaction between stakeholders involved in the creation and implementation of these alerts. These complex interactions should be the subject of future research efforts to understand the alert-implementation trajectory and identify the mediators for change and interventions to improve implementation.     

泮托拉唑临床应用的安全性评价与风险管理

目的了解泮托拉唑的不良反应及临床应用安全情况,加强泮托拉唑临床应用的风险管理。方法提取2014年在我院就诊并应用泮托拉唑患者的6 985张药物处方与同时间段使用奥美拉唑和兰索拉唑处方作为对照,收集并比较2组患者用药后一般不良反应的情况,并对泮托拉唑用药合理性进行评价。结果 1 018例患者服用泮托拉唑后出现不良反应,占14.57%,明显低于对照组(P<0.05),主要表现为头痛、头晕、乏力。试验组与对照组的高危患者泮托拉唑不良反应发生率均较高,肝肾功能不良患者不良反应发生率则明显低于对照组(P<0.05)。泮托拉唑致ADR中出现不合理用药占29.57%,其中超适应证是主要原因(P<0.05)。结论临床用药时应严格把握泮托拉唑的适应证,减少并避免药物滥用及超适应证用药。     

生物制品的致癌性评估及风险管理策略

大多数生物制品不会成为完全致癌物,但可以通过其药理学放大作用、免疫调节等成为肿瘤促长剂。在国际人用药品注册技术协调会（ICH）S1A和S6（R1）指导原则中对生物制品的致癌性评估有简单描述,但均缺少明确案例,且未考虑到新型技术药物的出现和监管思路的改变等情况。通过汇总2014—2021年美国食品药品监督管理局（FDA）批准的53项长期用药的生物制品的致癌性信息,并结合文献报道和实际工作经验,从生物制品的致癌性特点、致癌性评估策略、致癌性风险管理等几方面提出一些观点和建议,以期为国内同行、新药申报企业和审评机构提供有益的参考。     

湖北地区儿童监护人用药安全行为风险的KAP现况

目的：通过对湖北地区儿童监护人用药安全知识、态度和行为的调查，了解湖北地区儿童安全用药过程中存在的风险点及主要影响因素，为决策者制定减少居民用药错误相关干预策略提供依据，为药品安全科普干预内容和方法的精准设置，为今后药学知识传播的"供给侧"改革模式提供技术支撑。方法：借助湖北儿科联盟平台，以湖北省常住居民的用药行为作为研究对象，采用手机APP问卷调查和纸质问卷调查相结合的方法，以多中心研究形式，对目前监护人在儿童用药行为现状及风险水平进行大规模的调查。结果：收集有效问卷585份，主要以女性、19~49岁、在职城镇居民为主。主要问题集中在抗菌药物的应用、药品储存和过期药品的处理上，大部分受试者虽没有参加过各种形式的用药知识讲座或用药教育活动却认为有必要开展各种形式的合理用药知识教育活动。结论：根据此次问卷调查的结果，我们能很快发现湖北地区儿童用药安全行为的风险点，通过大数据分析评估公众在用药过程中的风险水平，医疗机构人员、教师、公司职员、机关干部更关注并了解药品安全的相关知识，但在湖北地区不论是农村还是城市，用药知识讲座或用药教育活动的开展都是不够的。我们今后在从事药品安全科普干预的过程中应注意根据受众的不同特点有不同的侧重点。     

Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions

PURPOSE: Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. METHODS: Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. RESULTS: The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p < 0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. CONCLUSIONS: Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts.     

Safety biomarkers and the clinical development of oncology therapeutics: Considerations for cardiovascular safety and risk management

During the clinical development of oncology therapeutics, new safety biomarkers are being employed with broad applications and implications for risk management and regulatory approval. Clinical laboratory results, used as safety biomarkers, can influence decision making at many levels during the clinical development and regulatory review of investigational cancer therapies, including (1) initial eligibility for protocol therapy; (2) analyses used to estimate and characterize the safety profile; and (3) treatment delivery, based on specific rules to modify or discontinue protocol treatment. With the increasing applications of safety biomarkers in clinical studies, consideration must be given to possible unintended consequences, including (1) restricted access to promising treatments; (2) delays in study completion; and (3) limitations to dose delivery, escalation, and determination of the maximal tolerated dose, the recommended phase 2 dose, and the optimal biologic dose selected for registration studies. This review will compare and contrast 2 biomarkers for cardiac safety that are employed in an increasing number of clinical programs designed for investigational oncology therapeutics: (1) assessment of left ventricular ejection fraction by either echocardiography or multigated acquisition scan; and (2) electrophysiological measurement of QT/QTc duration, assessed by electrocardiogram, for predicting risk of a potentially fatal arrhythmia called torsades de pointes. While these and other new safety biomarkers have major value in the development of oncology therapeutics, their applications require careful consideration to avoid unintended consequences that could negatively affect (1) the care of patients with advanced malignancy and (2) the advancement of promising new agents.     

Use of uncertainty factors by the European Commission Scientific Committee on Occupational Exposure Limits: a follow-up

Abstract

Decision on the safety margin, for instance by using uncertainty factors (UFs), is a key aspect in setting Occupational Exposure Limits (OELs). We analyzed the UFs in 128 OEL recommendations from the European Commission’s Scientific Committee on Occupational Exposure Limits (SCOEL). We investigated factors expected to potentially influence the UFs, as well as a selection of factors that might influence how expert groups perceive quality or reliability of key studies. We extracted UFs explicitly stated in the recommendations (EUFs) and, when EUFs were missing, calculated an implicit safety margin (ISM) by dividing the point of departure (PoD) by the OEL. EUFs and ISMs were lower for recommendations based on human data than those based on animal data. EUFs and ISMs were also lower for No-Observed Adverse Effect Concentrations (NOAECs) than Lowest Observed Adverse Effect Concentrations (LOAECs). We saw no differences based on local vs systemic critical effects. Acute data resulted in lower EUFs and ISMs than subchronic. We saw no influence from status of key study (publication status, performer or funder), but high tonnage substances (1,000,000+ tonnes) have lower EUFs and ISMs than substances currently not registered under REACH. Although SCOEL methodology stated that UF should be documented, only 65 out of 128 OEL recommendations included an EUF. Indeed, the ratio of EUFs to ISMs even decreased from 1991–2003 to 2004–2017. Additionally, EUFs were, on average, 1.8 times higher than ISMs. We conclude that a more articulate framework for using UFs could enhance consistency and transparency of the SCOEL recommendations.