抗抑郁药临床应用的进展

抗抑郁药是治疗抑郁症和抑郁症状的主要药物,近10余年来,从药物作用机制到药物的疗效和安全性得到了飞快地发展。使得治疗抑郁症和抑郁症状的药物具有更多的选择,为临床提高疗效、减少药物不良反应和减少疾病复发提供更多的手段。     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

Current and prospective treatments for multidrug-resistant gram-positive infections

Introduction: Staphylococcus aureus and Enterococcus spp. are two of the most common organisms causing nosocomial infections today; and are consistently associated with high mortality rates (approximately 20 and 44%, respectively). Resistance among these pathogens to first line agents such as methicillin and vancomycin continues to rise while isolates with reduced susceptibility to newer agents including linezolid and daptomycin continue to emerge, representing a serious concern for clinicians.

Areas covered: Mechanisms of action and resistance as well as in vitro and clinical experience in the treatment of resistant staphylococci and enterococci with currently available agents are discussed. Additionally, novel combination regimens showing enhanced efficacy and available data pertaining to prospective therapies including solithromycin, tedizolid, dalbavancin and oritavancin will be covered.

Expert opinion: With an increase in organisms displaying reduced susceptibility to vancomycin and the associated treatment failures, the significance of alternative therapies such as daptomycin, linezolid, ceftaroline, and prospective anti-gram-positive agents is on the rise. As our understanding of antimicrobial pharmacokinetic-pharmacodynamics principles continues to evolve, the selection of highly effective agents and optimization of dosages may lead to improved patient outcomes and delay the development of resistance.     

新型冠状病毒肺炎疫情防控常态化下临床试验用药品规范化应用的策略与实践

目的 分析福建医科大学附属协和医院在新型冠状病毒肺炎疫情防控常态化下临床试验用药品应用情况，优化管理策略，为其他药物临床试验机构提供参考。方法 对试验用药品全流程中的关键环节和存在问题进行探讨分析，制定疫情相关防控措施并优化流程，对比优化前后1年间的试验用药品应用情况、差错事件数和工作效率。结果 影响试验用药品应用的主要因素是人员、环境、流程，通过明确职责、加强培训和健全制度进行了流程优化。优化后2020年药物临床试验药房承担160项临床试验的药品管理工作，涉及随访受试者总数897名，负责应用259种临床试验用药品，工作量与2019年（128项）相比增长显著，工作服务能力有效提高，药品相关的差错事件发生频次显著下降（P<0.01），获得了研究者、申办方、监管部门等的高度认可。结论 新型冠状病毒肺炎疫情未对该院临床试验用药品应用造成持续影响，专人专职采用优化后的流程使疫情下试验用药品的应用更为规范，可保障受试者的用药安全，提高药物临床试验质量。     

Evaluation of anthrax vaccine safety in 18 to 20 year olds: A first step towards age de-escalation studies in adolescents

Background/objectivesAnthrax vaccine adsorbed (AVA, BioThrax^®) is recommended for post-exposure prophylaxis administration for the US population in response to large-scale Bacillus anthracis spore exposure. However, no information exists on AVA use in children and ethical barriers exist to performing pre-event pediatric AVA studies. A Presidential Ethics Commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds to older adults and if acceptable proceeding to evaluations in younger adolescents. We conducted exploratory summary re-analyses of existing databases from 18 to 20 year-olds (n = 74) compared to adults aged 21 to 29 years (n = 243) who participated in four previous US government funded AVA studies.MethodsData extracted from studies included elicited local injection-site and systemic adverse events (AEs) following AVA doses given subcutaneously at 0, 2, and 4 weeks. Additionally, proportions of subjects with ≥4-fold antibody rises from baseline to post-second and post-third AVA doses (seroresponse) were obtained.ResultsRates of any elicited local AEs were not significantly different between younger and older age groups for local events (79.2% vs. 83.8%, P = 0.120) or systemic events (45.4% vs. 50.5%, P = 0.188). Robust and similar proportions of seroresponses to vaccination were observed in both age groups.ConclusionsAVA was safe and immunogenic in 18 to 20 year-olds compared to 21 to 29 year-olds. These results provide initial information to anthrax and pediatric specialists if AVA studies in adolescents are required.     

人诺如病毒疫苗及治疗药物的研究进展

诺如病毒（norovirus,NoV）是引起急性胃肠炎的主要病原体之一,可以感染所有年龄段的人群。目前针对NoV引发的疾病尚无有效的治疗和预防手段,对于易感人群以及群发性感染,制定预防策略（包括疫苗）是必要的。利用NoV衣壳蛋白VP1以及VP1 P区域自我组装形成的病毒样颗粒是NoV疫苗的主要研究方向,通过基因工程技术设计的多种相关疫苗已在不同系统中表达,临床试验证明部分疫苗具有良好的免疫原性。此外,NoV与其他肠道病原体如轮状病毒的联合疫苗也具有良好的前景。此文重点介绍目前处于临床前以及临床研究的NoV疫苗以及NoV相关疾病的治疗药物。     

Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits

Introduction: Expanded access is the use of an investigational product by patients with serious medical conditions without participation in a clinical trial. It is a complicated process involving the collaboration of many parties and pharmaceutical companies. Ongoing efforts focus on accelerating expanded access procedures in the best interest of patients with cancer.

Areas covered: We review the regulatory and ethical challenges encountered in efforts to optimize expanded access.

Expert opinion: In the era of personalized medicine, patients may benefit from novel therapeutic agents that demonstrate encouraging results in early studies. However, drug approval is a lengthy and cumbersome procedure that might exceed the time frame of a life-threatening disease. Expanded access provides options to patients with unmet needs. It may provide informative safety and efficacy data to the manufacturers and the scientific and regulatory organizations.

Ongoing efforts are being made by global governmental and scientific committees, regulatory agencies, and patient organizations to address the ethical and regulatory issues and to optimize the expanded access process. Their goal is to expand access to promising novel drugs for individual patients and to accelerate the necessary procedures while preserving patient safety.     

靶向不同生物分子的抗银屑病新药的研究进展

随着对银屑病发病机制的深入研究,一些更具选择性的靶向不同生物分子的特异性新药相继出现.肿瘤坏死因子-α一直是银屑病治疗的关键靶点,新一代的抗肿瘤坏死因子-α药已研制成功.Th17细胞在银屑病的发生发展中起关键作用,已研制出靶向白介素-23/Th17轴的药物,包括白介素-12/23p40拮抗剂以及白介素-17、白介素-17受体和白介素-22拮抗剂.直接靶向T细胞的药物,如T细胞相关糖蛋白和肽酶以及靶向血管生成、趋化因子受体、神经生长因子和腺苷受体等治疗药已出现.概述目前处于研发阶段或正在进行临床试验的几类不同靶向的抗银屑病新药.