欧美原料药进口注册文件中的分析方法验证

目的:促进我国企业原料药的国际注册工作。方法:结合欧美原料药注册管理的要求,对其中的分析方法验证部分进行全面阐述,并提出具体的操作方法。结果与结论:分析方法验证无论在质量控制中,还是在国际药品注册活动中,都是非常重要的内容,我国企业必须给予高度的重视。     

Comparison of performance between rigid and non-rigid software registering CT to FDG-PET

Object: This retrospective study compares the anatomical accuracy of automated rigid and non-rigid registration software for aligning data from separately performed X-ray computed tomography (CT) and positron emission tomography with F-18-deoxyglucose (PET). Materials and methods: Analyses were performed on independently acquired PET and CT data from 40 tumor patients. Rigid as well as non-rigid automated fusion was carried out using the commercially available Mirada 7D platform (MIR and MINR, respectively) as well as a second automated non-rigid registration based on a variational image registration approach (VIR). Distances between lesion representation on PET and CT of 105 malignant lesions were measured in X-, Y-, and Z-directions. Statistical evaluation was performed using mixed effect analysis, comparing separately MIR with MINR and VIR with MINR. Results: The percentage of lesions misregistered by less than 15 mm varied from 70% for MIR and MINR in Z-direction to 93% for VIR in X-direction. The average X-, Y- and Z-distances ranged between 5.9 ± 5.7 mm for VIR in X-direction and 12.8±9.7 mm for MIR in Z-direction. MINR was significantly more accurate than MIR in Y-direction. Furthermore, VIR aligned thoracic lesions in the X- direction significantly better than MINR. Conclusion: The accuracy of rigid and non-rigid automated image registration can be expected to be better than 15 mm for the majority of lesions. Alignment tended to be more accurate with non-rigid registration. This work was supported by the ELAN-Fonds of the Clinical Faculty of the University of Erlangen-Nürnberg (AZ: 04.03.10.1) as well as by the Deutsche Forschungsgemeinschaft (DFG), Sonderforschungsbereich 603, Teilprojekt C10.     

临床试验注册制度与循证医学

本文介绍了当前新药临床试验、院内制剂、上市后药物临床试验及其他类型临床试验的管理情况,世界卫生组织临床试验注册平台(WHO ICTRP)的结构和运作机制和全球临床试验注册制度建立概况,中国临床试验注册中心和中国临床试验注册与发表协作网及其运作机制;提出用循证医学基本哲学思想作为临床试验研究者的思想和行为准则,是临床试验真实性的内部保障系统。     

US-MRI图像配准融合技术在高强度聚焦超声消融子宫肌瘤中的应用价值

目的 探讨超声和MRI图像（US-MRI）配准融合技术在高强度聚焦超声（HIFU）消融子宫肌瘤中的价值。方法 评估78例子宫肌瘤患者的80组US-MRI图像的配准与融合效果;记录并分析用于指导不同配准融合操作的解剖标记部位和效果。结果 以子宫的边界为标志配准同一子宫平面,与配准前比较,图像清晰度评分显著增加（P=0.004）;以子宫肌瘤的边界为标志配准同一子宫肌瘤平面,与配准前比较,图像清晰度评分显著增加（P<0.001）;以耻骨边界为标志能配准同一耻骨平面;以骶岬为标志点能配准骶尾骨。结论 US-MRI配准技术可有效提高HIFU消融子宫肌瘤的可视化空间。     

Report from the EPAA workshop: In vitro ADME in safety testing used by EPAA industry sectors

There are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data.     

美国临床试验数据库的信息建设及检索服务的研究

目的:探寻美国临床试验数据库的信息资源建立机制,为我国相关数据库的发展提供借鉴。方法:综述国外文献,研究数据库的组织结构,从信息数据建设和检索服务两方面对ClinicalTrials.gov进行研究。结果:该数据库具有较为独特和方便的组织结构和检索系统。结论:ClinicalTrial.gov作为世界上最有影响力的临床试验数据库,为患者、家庭成员、卫生保健专家以及社会公众的每一成员提供了获取各种疾病的临床试验信息的便捷途径,同时也对我国发展此类数据库有着重要的借鉴意义。     

全面实施预约挂号方便患者就医

2011年是深化医药卫生体制改革的关键年,首都医科大学附属北京朝阳医院按照北京市公立医院改革要求,结合医院门诊量快速增长所致医生工作强度大、患者挂号难、就医时间成本大等实际问题,通过增加预约号源、提高医生出诊率、拓宽门诊预约挂号渠道等多项措施方便患者就医,我院全面实施预约挂号以来取得了明显成效。     

Assessment of reproductive toxicity under REACH

The European REACH regulation requires the evaluation of reproductive toxicity in screening tests according to OECD TG 421 and 422 for substances above the tonnage level of 10 tons/year. The overall aim of this paper is to increase flexibility in combination with a reduced number of experimental animals. Therefore, in contrast to the existing approach the registrant should have the possibility to file a dossier for a substance at the level of 10 tons/year and above also on the basis of data from a developmental toxicity study (OECD TG 414) plus a full-scale subacute toxicity study (OECD TG 407 according to the 1995 protocol). The proposed new test strategy takes into account overall considerations of duty of care and animal welfare. It enables an assessment of developmental toxicity on a definitive instead of a screening level. Registrants should be allowed to select between these two options, either the existing approach (OECD TG 421/407 and alternatively TG 422) or the approach proposed in this paper (OECD TG 407 plus TG 414).     

托盘关联在基本药物核注核销过程中的应用

目的查找影响基本药物核注核销效率的因素,并提出解决办法。方法在生产线上增加后置工位,后置工位扫描托盘码,以建立大箱码与托盘码的关联关系。出库时直接扫描托盘码即可出库。结果使用托盘关联后,提高了基本药物核注核销的效率。     

Enhancing the quality of care for patients with breast cancer: Seven years of experience with a Dutch auditing system

Background

Hospitals in the Midwestern part of the Netherlands carried out a clinical audit to monitor the quality of breast cancer care during the years 2002-2008. Compliance with the National Guideline was investigated together with improvement in quality over time.

Methods

Patients with a malignancy of the breast (including ductal carcinoma in situ) participated in this study. Nine quality indicators were evaluated over the years. In 2004 and 2005 the hospitals also carried out an intervention project aimed at improvement of the efficiency of both the diagnostic process and the surgical treatment.

Results

At the end of the project all nine indicators showed significant improvement compared to the start of the project. Discussion of treatment strategy in a multidisciplinary breast cancer team took place more often before surgery (83% versus 56%) as well as after surgery (98% versus 70%). The National Guideline for maximum waiting times was met more often for the outpatient clinic (74% versus 61%), time to diagnosis (92% versus 82%), and surgical treatment (52% versus 34%). More sentinel node procedures were performed successfully (92% versus 69%), and for more patients more than 10 lymph nodes were evaluated in case of axillary lymph node dissection (85% versus 58%). More patients had definitive surgical treatment consisting of one surgical intervention (87% versus 75%), and left the hospital within 7 days after hospital admission (98% versus 66%).

Conclusion

The clinical audit contributed to improvement of the quality of breast cancer care in the Midwestern part of the Netherlands between 2002 and 2008.