药品上市后再评价的临床价值

1.创新药物研究.在国家十一五期间,令我国药学界科研工作者为之振奋的是国家投入了6亿人民币在重人新药创制的科研方面,这样给我们提供了机遇和挑战.在原创新药(化合物)开发的过程中.需经过化合物的合成与筛选,临床前的动物研究,临床人体试验Ⅰ～Ⅲ期,以及上市后的期Ⅵ期临床研究,才能从10000个活性化合物最终筛选出1个新药上市,而临床研究足决定创新药物研发成败的关键.     

药物相互作用早期临床研究在创新降糖药中的应用进展

摘 要 患者在同时使用多种药物时,常常会发生药物-药物相互作用（DDI）,其结果可能导致严重不良反应或改变治疗效果。在糖尿病治疗中,患者合用药物十分普遍,在创新降糖药上市前对其进行DDI临床研究十分必要,而现有的指导原则并未对创新降糖药的DDI临床研究设计和实施做出明确规定。目前该类研究在设计上呈现出多样性和复杂性的特点。现对创新降糖药DDI早期临床研究设计中的一些关键因素：研究类型选择、纳入人群和样本量确定、研究设计方法、给药方案、试验实施及试验结果进行综述,为创新降糖药的DDI早期临床研究提供参考。     

膀胱过度活动症治疗药物临床研究进展

膀胱过度活动症是一种临床常见病,对患者生活质量造成显著影响,药物治疗是重要手段之一.本文对近年来膀胱过度活动症治疗药物临床研究的进展进行了综述,分析了上市以及临床研发阶段抗胆碱药物、β3-受体激动剂的临床特点及应用趋势,包括A型肉毒毒素的临床研究情况,并对该类疾病治疗药物临床试验设计的关键要素进行总结分析,以期为临床研...     

免费接种,新冠疫苗怎么打

2020年最后一天,国药集团中国生物的新冠灭活疫苗获得国家药品监督管理局批准附条件上市(所谓附条件批准上市,是指用于治疗严重危及生命且尚无有效治疗手段的疾病以及罕见病的药品、公共卫生方面急需的药品,现有临床研究资料尚未满足常规上市注册的全部要求,但药物临床试验已有数据显示疗效并能预测其临床价值,因临床急需)。     

抗肿瘤纳米药物的临床转化进展及展望

纳米技术在肿瘤的治疗和诊断领域已显示出广阔的前景。目前有近80个抗肿瘤纳米药物处于临床研究阶段,多个产品获批上市,不仅增强了肿瘤治疗效果,并且降低了不良反应。然而,由于在相关的基础研究、生产控制和临床试验等方面存在诸多屏障,造成了转化率极低。本文从临床转化角度出发,综述了抗肿瘤纳米药物的发展、临床应用现状、面临的挑战与机遇,对纳米药物设计与临床试验策略方面进行了前沿性展望。     

治疗药物监测类体外诊断试剂临床研究浅析

目的 旨在阐述治疗药物监测类体外诊断试剂的临床研究要点.方法 结合体外诊断试剂现行法规和此类试剂自身特点,分析其临床研究的特殊要求.结果 对该类试剂的管理分类、研究方法、临床试验方案设置、临床试验样本选择、结果的统计学分析以及临床试验报告撰写等方面进行了详细解析.结论 治疗药物监测类体外诊断试剂的临床研究应从试剂本身的临床预期用途出发,科学、合理、完整地对试剂进行临床验证.     

中国附条件批准政策梳理及抗肿瘤创新药审评标准浅析

为了鼓励以临床价值为导向的药物创新,现行《药品注册管理办法》明确提出了4种加快上市注册的程序。对于早期临床试验数据可证实药物疗效并能预测其临床价值的创新药,经评价后可以通过附条件批准工作程序,在完成确证性临床研究之前上市,让有严重危及生命且尚无治疗手段的患者获得更多延长其生命或改善其生活质量的治疗机会。附条件批准工作程序可以缩短药品上市前的临床研发时间,因此其配套政策和审评标准备受关注。本文以肿瘤创新药为切入点,对我国附条件批准的政策要求和审评过程中已经形成的标准进行系统的梳理,并尝试对附条件批准实施过程中遇到的问题进行分析并提出建议,供业界参考。     

新药发现阶段药物毒理学研究的策略与方法

随着重大创新药物创制专项的实施,我国创新药物研发的数量将步入稳定上升期。纵观整个药物研发流程,从药物发现、临床前研究、临床研究直到药物上市,药物毒理学研究贯穿始终,并起着非常重要的作用。鉴于创新药物发现阶段药物毒理学地位和作用的日益突出,文中就相关研究的策略与方法作简要阐述。     

家兔经皮给药安全性评价研究方法的探讨

近年来,经皮给药因具有避免肝脏的“首关效应”、保护胃肠道免受药物损伤、血药浓度持久恒定等优势而备受青睐。而药物临床前安全性评价研究对新药临床研究,以及上市前审批过程中均起重要的作用。以《药物非临床安全性评价指导原则》为依据,结合多年的研究经验,从实验动物、剂量设置、给药量的换算、皮肤去毛及破损模型制备、指标评价等多个方面对家兔经皮给药的安全性评价研究方法进行探讨,为经皮给药的受试药物安全性评价研究提供方法参考。     

英国药物临床试验审评审批机制的研究

通过查阅英国药物临床试验法律法规、指南、相关文献,并对历年绩效数据进行统计后发现,英国药物临床试验审评时限比较注重科学性和灵活性,对技术审评与伦理审查程序采取并行的安排,并建立了上市后临床研究和研究者发起的科研性临床研究的审查机制等内容值得我国借鉴。我国现行药物临床试验管理制度,较好地保证了受试者的安全,但仍要把握对临床试验制度要素的控制,不仅在程序上要层层把关,还要尽可能提高审查的效率,使新的疗效好的药物尽快在我国上市,以满足我国人民的用药需求。     

Analysis of information submitted by clinical trial sponsors regarding the safety of investigational drugs

During performance of clinical trials in medical institutions, information regarding the safety of investigational drugs is submitted by trial sponsors according to guidelines for good clinical practice. In the present study, reports of clinical trials conducted at the University of Tokyo Hospital were examined, focusing on the safety information provided to the Institutional Review Board (IRB). Two hundred two reports (52 protocols) of safety information were submitted to the IRB by clinical trial sponsors between April 2000 and March 2001, of which 185 contained a total of 3021 cases of adverse events. Of those, 194 reports were judged by clinical investigators/physicians not to be associated with any significant problems and the trials were continued. For 157 of those 194 reports, it was considered unnecessary to inform the test subjects of the report contents, including the adverse events. The decision of whether or not the test subjects should be informed of such contents tended to depend on the causal relationship between the adverse events and drug intake, as well as the predictability of the adverse events. For 8 of those 194 reports, the IRB recommended that the clinical investigators/ physicians provide information to the test subjects and/or submit detailed information on the status of these subjects to the IRB. From these results, we suggest that establishment of a system to unify and evaluate drug safety information is necessary to provide safe and efficient clinical trials.     

Scientific drug safety information for patients' consent

One of the important roles of pharmacists is to continue their contributions to new drug discovery and development. However, it seems to be very difficult to obtain patient satisfaction with new drugs. Because new medicines have both benefit and risk, there should be many systems to maximize the safety and efficacy of the drugs. In clinical trials, the rights, safety and welfare of human subjects under the investigator's care must be protected. Good Clinical Practice is a harmonized ICH-guideline, and the safety information of an investigational product is explained to patients who voluntarily enter the clinical trials. Since safety information about investigational products is still limited, subjects are informed about the results of animal experiments and those of finished clinical trials. The sponsor of clinical trials should be responsible for the on-going safety evaluation of the investigational products. When additional safety information is collected in the clinical trials, the written informed consent form should be appropriately revised. During the review process, quality, safety and efficacy of new drugs are evaluated and judged based on the scientific risk-benefit balance. The safety information collected in clinical trials is reflected in the decision-making process written in the review reports. All-case investigation should be also performed until data from a certain number of patients has been accumulated in order to collect early safety and efficacy data. Important messages written in review reports for drug safety and patient consent are explained. Risk communication will improve the application of patients' consent for new drugs.     

Improving safety reporting from randomised trials.

Randomised clinical trials offer a unique opportunity for capturing safety information under a controlled setting that minimises biases in the comparison of different therapeutic options. Nevertheless, empirical evidence across diverse medical fields suggests that the reporting of safety information in clinical trials is largely neglected and receives less attention compared with efficacy outcomes. An analysis of 192 randomised trials has shown that reasons for withdrawals due to toxicity were specified per study arm in only 46% of the trial reports. Adequate reporting of clinical adverse effects and laboratory-determined toxicity occurred in only 39 and 29% of the trials, respectively, even with lenient definitions of what constitutes adequate reporting. The use of standardised scales for adverse effects is a prerequisite for improved reporting on safety in randomised trials. Safety data need to be collected and analysed in a systematic fashion and active surveillance for toxicity during the conduct of a randomised trial is preferable to passive surveillance. Standardised reporting of safety data does not necessarily require extensive space to accomplish. It is essential to provide numerical data per study arm on each type of adverse effect along with a categorisation of the severity of the adverse effects with an emphasis on severe and life-threatening reactions. The severity grading must be referred to well-known standardised scales and new scales need to be carefully defined. Information on withdrawals due to toxicity is also important to report, along with the specific reasons leading to discontinuation. Tabulation of information may be helpful and rare or not previously reported adverse effects should be described in detail. The availability of newer options such as electronic publication, publication of raw databases, large database research, meta-analytic approaches, and prospective registration of clinical trials and of their databases may further improve the safety insights we can gain from randomised clinical trials.     

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.     

Design, monitoring, and analysis issues relative to adverse events.

In the clinical development of new drugs for market approval, it is frequently impossible to design trials to provide definitive information about safety--particularly about adverse events. It is possible, however, to design most trials to provide definitive information about efficacy. Efficacy trials with new drugs should therefore be monitored for safety, and the safety profile described within and across trials. Confidence intervals are recommended as the appropriate statistical methodology for doing this. Such intervals provide an interval estimate on the unknown incidences of adverse experiences among patients who could be treated with each regimen, as well as permit a conclusion that two regimens are different.     

信息追溯技术在临床试验用药品全生命周期闭环管理中的应用浅析

加强临床试验用药品的闭环管理,对提高临床试验用药品管理质量,保证受试者用药安全具有重要意义.本文通过文献调研临床试验用药品生产制备、流通、回收和销毁等各环节的管理现状及临床试验用药品全生命周期的信息化管理现状,结合同济大学附属杨浦医院在临床试验用药品流通管理过程中发现的问题,提出信息追溯技术在临床试验用药品全生命周期闭...     

FDA对研究者在新药和医疗器械临床研究期间安全性报告的要求

上市前药物和医疗器械安全性信息主要来自临床试验,而观察受试者对试验药物和器械反应的是研究者,因此,研究者的不良事件报告至关重要。为帮助研究者确认临床研究期间非预期的安全性信息并遵守安全性报告要求,美国食品药品管理局（FDA）于2021年9月发布了“研究者职责-研究性药物和器械的安全性报告”指导原则（草案）,详细说明了对研究者在IND和IDE研究中向申请人和伦理委员会报告的要求。我国目前还没有类似的指导原则,详细介绍FDA的该指导原则,以期对我国新药和新医疗器械研究者在临床研究期间识别非预期的安全信息并按要求及时报告有帮助并对该方面的监管有所启示。     

中药注射剂临床安全性评价研究进展

由于中药上市前研究目的比较单纯、实验人群范围比较窄、用药时间较短等原因,很难得出药品全面的安全性数据,这不利于药品上市后的合理安全的应用。安全性再评价是中药上市后再评价的首要环节,该文通过查阅文献资料,对参麦注射液、丹红注射液、参芪扶正注射液等中药注射剂目前的安全性研究作一综述,为临床合理用药提供参考。     

药物临床试验各环节的风险管理

随着我国创新药物研发能力的不断提高,新药临床试验的数量也在不断增加。新药临床试验是验证药品有效性和安全性的关键环节,其结果的可靠性直接关系到百姓的用药安全。临床试验的完成质量受多方因素的影响,其中临床试验机构的管理起重要的作用。通过分析药物临床试验各环节的质量风险因素,并探讨了降低风险的应对措施,以期为药物临床试验的质量管理以及项目质量的提升提供借鉴。     

The role of scientific evidence of risks and benefits in determining risk management policies for medications

Recent changes in the regulatory environment have called attention to the need for and potential benefits of greater and more detailed evidence to inform decisions based on the risk-benefit profile of medications. Nevertheless, access to potentially beneficial therapies continues to be impeded by a lack of sufficient information that could help optimize benefits and minimize risks of treatments for patients. Over-reliance on pre-marketing clinical trials and the FDA's spontaneous reporting adverse event system to support regulatory decisions has sustained an information void. Clinical trials are the gold standard for demonstrating efficacy, but they cannot fully predict safety when drugs are used in the real world. Spontaneous reporting can identify new signals, but cannot quantify those signals or place them in appropriate clinical context. In the face of new safety signals, absence of better information on how medications are used and how they perform in the real world setting, regulators are often limited to either continuing drug marketing without significant changes or withdrawing a medication from the market. Experience shows that information collected proactively, to better understand the background risks associated with the underlying disease and to better quantify the product risks, can influence these decisions to include a wider range of options regarding a product's availability, labeling and additional risk management strategies. This article presents several case studies of medications, including those in which insufficient data were available to address important safety signals and decisions were made to withdraw products, as well as those in which epidemiologic data were available to provide reassurance of product safety and allow continued product use, even though some may be marketed with additional risk management programs. More extensive and earlier epidemiologic assessment of risks and benefits of new products will create a new standard of evidence for industry and regulators and is likely to result in more effective and balanced regulatory actions, thereby affording better care for patients.