In the past decade,with the implementation of policies to promote the research and develop-ment of rare disease drugs,the increase in the number of clinical trials for rare disease drugs has posed new challenges to ethical review.Clinical trials of rare disease drugs involve vulnerable populations with a small number of patients,scattered populations,and relative concentration in certain disease areas.The trials are mainly conducted in the early stages,often requiring small sample sizes,single arm designs,and more new technologies such as cellular and gene therapy.In addition to meeting the general requirements of clinical trials for common diseases,ethical review should also give special attention to the special characteristics of rare disea-ses in risk benefit assessment,research design,informed consent,trial operation,etc.Ethical review of clinical trials for rare diseases should effectively promote the development of new drugs for rare diseases and protect the rights and interests of participants.By analyzing the characteristics of clinical trials for rare diseases drugs,this paper presents the points of special concern during the review,aiming to improve the level of ethical review for clinical trials of drugs related to rare diseases.

目的 为检验伦理审查互认的实施效果,北京市卫生健康委员会决定对联盟中25家具备主审资质的医疗机构进行现场督导检查,为此联盟制定了伦理审查互认现场督导检查的评分标准,以保证检查的客观性和一致性.方法 评分标准主要参考《北京市医学伦理审查互认联盟工作规则》及25家医疗机构前期基本调研情况制订.结果 评分标准由3个一级指标、10个二级指标和13个三级指标构成.3个一级指标分别为制度建设(30分)、互认情况(25分)和审查效率(45分).结论 评分标准为北京市医学伦理审查互认推进的重要工具,尽管个别指标在现阶段有使用上的局限性,但总体能较全面地考察伦理审查互认的实施情况及效果,且有一定可操作性.

Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions: Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

In order to achieve the overall victory over 2019 novel coronavirus disease epidemic, especially to prevent the disease recurrence from rebounding during the resumption of labor, the government has not loosened any control of personnel mobility, which has obviously affected the normal examination and treatment of lung cancer patients under the influence of this epidemic. During the epidemic period, cancer patients with low immunity levels face the double ordeals of disease and epidemic situation. Compared with the general population, they are more likely to be infected with the new coronavirus. Among the infected cancer patients, lung cancer is the most common type. It is necessary to provide more appropriate individualized treatment recommendations for patients with lung cancer based on the epidemic situation of the patient's location and in combination with the patient's own condition. Through active prevention of infection, timely conversion of treatment strategies, online and offline joint control, and positive psychological counseling, we do our best to help patients with lung cancer to survive this difficult period.

本文由中国临床研究能力提升与受试者保护高峰论坛(CCHRPP)组委会邀请多位临床试验行业的资深专家,组成工作委员会,以目前新型冠状病毒感染为样本,讨论并达成《重大突发公共卫生事件(传染性疾病)一级响应下临床试验管理共识(2.0版)》,供GCP从业人员参照实施.共识从整体原则、核心准则、基本策略、工作开展、伦理审查、疫情防护、各方沟通及文件记录八个方面阐述了要点.

微生物群是由栖息在人体口腔、肺、肠道等部位的细菌、病毒和真菌等组成的一个复杂生态系统，在人体健康和疾病中发挥了重要作用。其中研究最多的是细菌，细菌菌群失调与包括恶性肿瘤在内的多种疾病的发生、发展和宿主免疫系统的调节相关。肺癌是发病率和死亡率增长最快、对人类健康和生命威胁最大的恶性肿瘤之一，肠道和肺部细菌菌群可能在肺癌的诊断及治疗中发挥了作用。本综述简要介绍目前细菌菌群与肺癌诊治关系的研究现状。.

罕见病由于诊断治疗困难,在全球范围内都是影响人类健康的重要问题.近年来罕见病的临床研究不断增多,但研究相关的伦理学问题容易被忽视.本文通过分析罕见病人群和罕见病研究的特点,提出罕见病临床研究需要从研究的目的、方案设计、风险收益分析和知情同意等不同环节关注伦理学问题,旨在提高研究者的伦理意识,帮助伦理委员会开展相关审查,最终提高罕见病临床研究的伦理水平.

无论罕见病还是常见病,缩短药物研发上市的时间是各方的共同需求,这对于大多数尚无有效治疗方法的罕见病而言尤为重要.美国罕见病药物相关激励政策出台时间最早,因此罕见病药物临床试验数量最多,中国的临床试验数量正在逐渐增加.罕见病的药物临床试验以罕见肿瘤为主,目前多为Ⅱ期试验.临床试验作为孤儿药研发中的重要环节,除需要政策支持,在试验设计和实施中还存在很多问题,如对自然病程和发病机制缺乏了解、无法实施随机对照试验、有待更为新颖的试验设计和敏感的终点指标、入组困难、存在伦理冲突等.这些问题的解决有待政府部门、制药企业、医疗机构、患者组织等多方努力才能共同实现.

人类遗传资源是孕育尖端生物科技的知识宝库、是精准医学的基石.随着基因诊断及个性化诊疗的推进,涉及人类遗传资源的研究激增.人类遗传资源人格与财产、物质与信息的双重属性也给伦理审查带来了挑战.涉及遗传资源研究伦理审核的难点主要包括如何落实知情同意和如何做好受试者保护、如何平衡个体与家庭的利益、处理概括同意与具体同意的关系以及受试者获益等.在此基础上,提出相关医学伦理困境的反思与解决策略:健全现有法律体系,提升人类遗传资源管理文件的效力层级;完善人类遗传资源管理的条款及规定,将知情同意法律化;完善伦理治理规范,利用规范的灵活性对不宜写入法律的有关内容进行约束;应明确规定权利主体及人类遗传资源开发利用所衍生权益归属问题,遗传资源保护与技术共赢"两手抓,两手都要硬".

Objective To evaluate the efficacy and safety of higenamine hydrochloride(HG) stress echocardiography for diagnosis of coronary artery disease (CAD). Methods The study was designed as prospective,randomized,open-labled,positively controlled and crossover phase II multi-center clinical research.Ninety subjects who were suspected to have CAD were enrolled.HG dosage was titrated at 0.5,1, 2,4 μg.kg -1.min-1every 3 min.Adenosine was injected 140 μg.kg -1.min-1for 6 min with total dosage 0.8 mg/kg.Visual assessment of the left ventricle wall motionand 17-segment model were used for analysis of stress echocardiography.CAD was defined as identifying >50% diameter stenosis in at least one major coronary artery by coronary angiogram.All adverse reaction were recorded. Results For HG group,the sensitivity,specificity,accuracy,positive predictive value and negative predictive value were 28.9%,89.7%, 57.1%,76.5% and 47.8%,respectively;for adenosine group,they were 26.7%,94.9%,58.3%,85.7%and 47.1%,respectively. There was no significant difference between the two groups( P > 0.05). The diagnostic sensitivities of HG and adenosine echocardiography for single vessel stenosis were 11.1% and 5.6%,respectively( P >0.05).Both HG and adenosine echocardiography have the same sensitivity with 37.5% for double vessel stenosis and 44.4% for triple vessel stenosis.Advers reaction rate was 84.4% in HG group and 92.2% in adenosine group( P >0.05).Conclusions HG stress echocardiography for CAD diagnosis has high specificity,good safety and low sensitivity,which are similar to adenosine echo.

Objective:To analyze the time consumption in the review of multicenter clinical trials and to explore the methods of improving the approval efficiency.Methods:We retrospectively analyzed 246 multicenter clinical trials approved by our hospital from 2012.Group A were trials that our hospital was the leading site while group B were those not.In group B,trials were divided into group B1 (conference review) and B2 (expeditedreview)according to the ethical review methods.Each group's ethical review time,contract signature time,starting experiment time,the total time consumption of review,and the time from the leading site approving to the participating site submitting application were analyzed.Results:In the review of multicenter clinical trials,contract signature cost the most time,accounting for 41％.There was no significant difference in terms of whether to be the leading site.The total time consumption of group B1 and group B2 was 180.94 days and 140.36 days (P ＜0.05),respec tively.The average ethical review time of group B1 was about 20 days longer than group B2 (P ＜ 0.01).There were 96.54 days that the leading site submitted review materials to the participating site after approved.Conclusions:In multicenter clinical trials,for those the leading site has already approved,immediate submission to participating site and choosing the expedited review method may improve the ethical review efficiency,thereby shorten the total approval time consumption.

目的 通过分析药物临床试验项目伦理审查各环节的耗时情况,探讨提高审查效率的可能途径.方法 以在我院药物临床试验伦理委员会审查并拿到批件的99个药物临床试验项目为研究对象,针对会议审查和快速审查项目,分别采集审查各个环节所需时间进行分析.结果 会议审查及快速审查项目的平均审查时间分别为43.7和40天,在一个月内完成审查的项目占40％,绝大多数项目在2个月内完成伦理审查;在伦理审查的各个环节中,从上会到拿到批件耗时最长,约占审查总时长的53.6％.预审环节平均消耗时间为2.1～2.3天;伦理审查过程中,申办方及研究者所用的时间明显多于伦理委员会消耗的时间,在会议审查及快速审查中,申办方及研究者与伦理委员会的耗时比分别为1.69及3.8.结论 在伦理审查的过程中,申办方、研究者及伦理委员会须各尽其责、加强沟通,以提高伦理审查效率.

Objective To analyze the present situation of the application of CT in third-grade hospitals in Beijing. Subjects and Methods Analyzed the application conditions of CT equipment in 42 third-grade hospitals in Beijing, including the brand, model, quantity, scanning technical requirements, image requirements, film observation requirements, and radiation dose. Results CT scanning in these hospitals are in good condition, problems mostly come from the scanning mode, image quality, dose control, and the use of films. Conclusion The usages of CT in third-grade hospitals in Beijing are reasonable, but strengthened monitoring and continuous improvement of image 100053, China; 3. Fu Wai Hospital, Chinese Academy of Medical Science, Beijing 100037, China;4.Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China; 5. People’s Liberation Army Air Force General Hospital, Beijing 100142, China&nbsp;quality are still necessary.

Objective This study is to investigate the relationship between different coronary computed tomography angiography (CCTA) examination modes and the radiation dose, in order to achieve as low as reasonable radiation dose, guiding and regulating the legitimation and optimization of coronary CTA examination. Materials and Methods Analyzed the effects of different models of MSCT and different scanning modes for coronary CTA on radiation dose in 30 tertiary hospitals of Beijing. All cases were divided into different groups according to CT models (general 64-slice CT and post 64-slice CT) and scanning modes (prospective ECG-triggering axial acquisition mode, retrospectively ECG-gated spiral data acquisition mode and prospectively ECG-gated high-pitch spiral acquisition mode). Achieved the mean values of CTDI, DLP and ED respectively and using independent sample t-test to analyze the radiation dose difference between different models and scanning modes. Results The statistical data on CTDI, DLP and ED of the post 64-slice CT is(27.61±19.61)mGy、(412.56±328.74) mGy?cm、(5.78±4.60) mSv, respectively, lower than those of the general 64-slice CT (57.09±27.58 ) mGy、(950.93±552.91) mGy?cm、(14.53±8.81) mSv, and the difference was statistically significant (P<0.05). The mean values of CTDI,DLP and ED were (17.98±11.27) mGy、(229.63±158.31) mGy?cm、(3.24±2.20) mSv in the prospective ECG-triggering axial acquisition mode group, retrospectively, while the mean values of CTDI, DLP and ED in ECG-gated spiral data acquisition mode group were (50.89±25.01) mGy、(839.80±469.56) mGy?cm、(12.40±7.42) mSv, respectively , the difference was statistically signiifcant (P<0.05). Conclusion Post 64-slice CT and low-dose scanning mode are both helpful for radiation dose reduction in coronary CTA.

目的 探讨双源CT(DSCT)冠状动脉成像有效辐射剂量(ED)、图像质量与心电门控技术和扫描管电压(kV)的关系.方法 对101例(男42例,女59例,平均年龄60.2岁±10.8岁)DSCT冠状动脉血管成像的连续患者行回顾性研究,所有患者均未口服或静脉给予β受体阻滞剂、硝酸甘油等控制心率和扩张血管药物.本组根据前瞻性心电门控(44例)和回顾性心电门控(57例)(组1),以及扫描电压100 kV(43例)和120 kV(58例)(组2)分成2组,对组1、2的图像质量(1～4分)和有效辐射剂量(mSv)分别进行组间对比研究.组间计量资料采用t检验,计数资料采用χ2检验.P<0.05为有统计学差异.结果 本组仅1例因扫描过程中出现心律失常导致检查失败(技术成功率99%).组1前瞻门控组和回顾门控组冠状动脉图像质量平均分分别为3.3±0.5和3.3±0.3(P>0.05),图像噪音分别为(20.9±5.1) HU和(23.9±6.5) HU(P0.05),图像噪音分别为(25.2±7.0) HU和(20.6±4.5) HU(P<0.001).结论 在不降低双源CT冠状动脉检查成功率和图像质量的情况下,采用前瞻性心电门控和100 kV管电压扫描,能够显著降低患者的有效辐射剂量.

Objective To analyze the image quality of coronary arteries by dual-source computed tomography (DSCT) in children with congenital heart disease(CHD). Methods Image quality of coronary arteries were scored by two radiologists with an ordinal grading system. Score 3 or 4 was considered to be good image quality and diagnostic. Score differences among 3 groups of various baseline heart rate levels, 3 groups of various age levels and 4 coronary branches were analyzed by using ANOVA. Multiple linear regression analysis was used to test the effects of age, heart rate, tube voltage, tube current, pitch, contrast volume, contrast injection rate on the coronary image scores. Results A total of 72 consecutive patients were enrolled. 71.2% (205/288) of coronary artery branches was good enough for diagnosis. Image quality of left main coronary artery (LM, score 3.64±0.49), left anterior descending (LAD, score 2.97±0.40), right coronary artery (RCA, score of 2.82±0.70), left circumflex (LCX, score 2.76±0.73) were in a descending order (F=29.00, P<0.01). Image scores of age groups of 0--1 years old (2.80±0.65), >1--3 years old (2.81±0.74), >3--14 years old (3.58±0.52) were in an ascending order (F= 20.16,P<0.01). Image scores of heart rate groups of<100 bpm (3.54±0.56),100--150 bpm (2.86± 0.70) and >150 bpm (2.81±0.63) were in a descending order (F=16.72, P<0.01). Multiple linearregression analysis demonstrated that multiple impact factors affected image quality of LM, LAD, LCX and RCA. Age(r=0.013 ,P<0.01)and contrast volume(r=0.292, P<0.01)had positive correlation with LM score. Age(r=0.509, P<0.01) and voltage (r=0.292, P=0.011) had positive correlation with LAD score. Heart rate(r= -0.179, P<0.05) had negative correlation with LAD score. Age (r=0.063, P< 0.01) had negative correlation with LCX score. Age (r=0.486,P<0.01) and voltage (r=0.220, P<0.05) had positive correlation with RCA score. Conclusions Dual-source CT could clearly shows coronary arteries of children with CHD over the age of 3 or with heart rate less than 100 bpm. Limitations of Dual-source CT coronary angiography for CHD children included young age and fast heart rate.

> 患者男,34岁,因胸痛3个月来诊。3个月前无诱因出现隐隐胸痛发作,部位不固定,最长可持续1 d。患者平时长时问活动耐力差,短时间活动耐力未见异常,无心肌梗死、心内膜炎、风湿性心脏病、肺结核等病史。体检:血压120/80 mm Hg(1 mm Hg=0.133 kPa),皮肤黏膜未见异常,口唇略红润,颈静脉无怒张。心界不大,心脏各听诊区未闻

Objective:To improve the understanding of cardiovascular involvement in Behcet's disease(BD). Methods:The Echocardiographic manifestations on 69 in-patients with BD in our hospital were analyzed retrospectively. Results:52.2%(36/69 ) patients showed abnormal echocardiographic findings,in those patients,valvular regurgitation (61.1%),pericardial effusion(41.7%),pulmonary artery hypertension(38.8%) and enlarged heart chambers(36.1%) were more common.Aortic dilation,cardiomyopathy,old myocardial infarction and intracardiac thrombus were also found in those BD patients. Conclusion:There were many echocardiographic manifestations in BD patients.The principle findings were aortic valve prolapse, perforation,tear and regurgitation,those pathologic changs especially combined with valvular ring perforation,dilated aorta and aortic dissection.Pulmonary artery pressure should be measured in every BD patient.Echocardiography played an important role in the diagnosis and follow-up examination in BD patients for their cardiovascular involvements and transesophageal echocardiography could provide additional information in some cases.

Objective To evaluate the diagnostic values of MSCT for detecting atherosclerotic plaques on New Zealand rabbits models in comparison with pathologic results. Methods Fifteen New Zealand rabbits were enrolled in this study, including 5 with balloon injury and high-fat diet ( group A), 5 with high-fat diet only (group B) and 5 with regular feed (group C). 16th week late, contrast-enhanced MSCT scan was performed in all rabbits with 16 slice MSCT (16-MSCT) in group A and 64 slice MSCT (64-MSCT) in group B and C. The CT and pathological findings were compared in a double-blind manner. The sensitivities and specificities of 16-MSCT and 64-MSCT for detecting atherosclerotic plaques were evaluated by using Fisher test and x2 test. Results Sixty and seventy-five images on 16-MSCT and 64-MSCT had corresponding pathological slices. The sensitivities for the detection of plaques on 16-MSCT and 64-MSCT were 41.5% (22/53) and 64. 9% (24/37), and spocificities of 85. 7% (6/7) and 89. 5% (34/38), respectively. Conclusions 64-MSCT has a higher sensitivity in the detection of atherosclerotic plaques than 16-MSCT. Both scanners can be used to preclude the diagnosis of atherosclerosis.

遗传性出血性毛细血管扩张症(HHT)合并弥漫肝动静脉瘘和肺动脉高压的HHT 1例报道. 1 病例资料 患者女,34岁,活动气短1年余,伴有咯血6个月.略暗红色血块,无胸痛、发热及咳痰.入院查体:两手指尖皮肤毛细血管扩张.双肺呼吸音清,无干湿啰音.P2>A2,P2亢进、分裂.双下肢不肿.血气分析无异常,低于正常值的生化指标有:红细胞总数2.96×1012/L,血红蛋白74 g/L,总蛋白55.0 g/L,白蛋白32.0 g/L,血小板计数110×109/L.