《药物临床试验质量管理规范》培训的思考

医务人员是临床试验的主要设计者和参与者,普及《药物临床试验质量管理规范》(GCP)有助于提高医务人员临床试验的水平规范临床试验的管理,保护受试者的合法权益及健康安全,提高临床试验结果可靠性,从而提升我国医疗机构进行临床试验的能力,促进医药相关产业的发展.从建立临床试验职业资格准入制度和监督管理机制、将《药物临床试验管理规范》(GCP)培训纳入继续教育体系2个方面进行了探讨,提出了加强医务人员GCP培训的途径和建议.     

对我国药物临床研究受试者权益保护的法理学思考

目的探讨药物临床研究受试者权益保护问题。方法分析药物临床研究受试者的弱势地位,并从法理学角度探讨保护药物临床研究受试者权益的必要性及理论基础。结果与结论我国GCP规定了受试者的诸多权利,体现了对受试者的倾斜性保护,这是实现实质平等的客观需要,也是保护其权益的有效方式,但仍存在瑕疵,应在修法中不断完善。     

医院药物临床试验免费检验信息系统改进的探讨与实践

目的 通过建立契合医院实际的药物临床试验（drug clinical trail,DCT）免费检验信息系统（laboratary information system,LIS）,方便研究医师开展实施DCT,体现药物临床试验质量管理规范内涵要求。方法 结合医院现行的诊疗流程,了解医院普通医嘱组套的实施过程。与信息科工程师沟通DCT医嘱组套的实现形式以及在系统中与普通医嘱的区别点。并通过前期试运行的结果,逐步改进和完善医院的DCT免费LIS。结果 建立了适合医院的DCT免费LIS,降低了临床医师开具实验室检查单的差错率,提高了试验项目中的检验检查正确率,减少了检验检查的缺漏项。结论 电子免费LIS与纸质检验检查申请单相比,在准确度、结果回报和溯源方面都具有优势。     

构建中医肝病新药临床试验研究技术平台探索

通过中医肝病临床新药伦理委员会、实验方法学、疗效评价、数据管理等技术平台的建设,及相关技术平台的建设,构建符合中医肝病疗效特点的新药临床评价方法和指标体系,从而搭建符合国际GCP 规范的中医肝病新药临床试验技术平台。     

50年来我国抗肿瘤药物临床研究的进展

自从20世纪50年代肿瘤逐渐成为卫生工作的重点之一,抗肿瘤学新药的研制也随之开始。但由于没有合适的指导原则,在早期发展缓慢而且受到干扰。从80年代以后卫生部药政局制定了新药开发的GCP指导原则,有些有效新药经过临床试验进入市场为患者服务。10年前我国食品药品监督管理局成立以后,近年来每年临床试验的数目超过100项,有些是国际多中心临床研究。我国开发了肿瘤新生血管抑制剂恩度和参一胶囊,从中药提取的有效成分康莱特和β榄香烯等都已经上市。新的靶向药物尼妥珠单抗和埃克替尼正在进行临床试验。在过去50年间我国共开发12项能改善临床实践的新药或新方法,已经给患者带来裨益。通过中西医融合,对肿瘤治疗的个体化“同病异治”和“异病同治”将有我国的贡献。应当优先发展抗肿瘤新药,创新挽救患者。     

我国药物临床试验法规与相关国际法规的对比研究

文中通过比较我国药物临床试验法规与相关国际法规的差异,对两者之间存在的临床试验批准、临床试验机构选择、伦理委员会的设置、受试者损害补偿机制、不良事件监控体系和受试者招募广告6个方面的差异进行了分析,并针对上述差异提出了相关的建议,从而使我国的临床试验研究政策与国际接轨,提高我国药物临床研究的水平。     

N-substituted glutamyl sulfonamides as inhibitors of glutamate carboxypeptidase II (GCP2)

Glutamate carboxypeptidase II (GCP2) is a membrane-bound cell-surface peptidase which is implicated in several neurological disorders and is also over-expressed in prostate tumor cells. There is a significant interest in the inhibition of GCP2 as a means of neuroprotection, while GCP2 inhibition as a method to treat prostate cancer remains a topic of further investigation. The key zinc-binding functional group of the well-characterized classes of GCP2 inhibitors (phosphonates and phosphoramidates) is tetrahedral and negatively charged at neutral pH, while glutamyl urea class of inhibitors possesses a planar and neutral zinc-binding group. This study introduces a new class of GCP2 inhibitors, N-substituted glutamyl sulfonamides, which possess a neutral tetrahedral zinc-binding motif. A library containing 15 secondary sulfonamides and 4 tertiary (N-methyl) sulfonamides was prepared and evaluated for inhibitory potency against purified GCP2 enzyme activity. While most inhibitors lacked potency at 100 μm, short alkyl sulfonamides exhibited promising low micromolar potency, with the optimal inhibitor in this series being glutamyl N-(propylsulfonamide) (2g). Lastly, molecular docking was used to develop a model to formulate an explanation for the relative inhibitory potencies employed for this class of inhibitors.     

Effects of mass consciousness: changes in random data during global events

A long-term, continuing experiment is designed to assess the possibility that correlations may occur in synchronized random data streams generated during major world events. The project is motivated by numerous experiments that suggest that the behavior of random systems can be altered by directed mental intention, and related experiments showing subtle changes associated with group coherence. Since 1998, the Global Consciousness Project (GCP) has maintained a global network of random number generators (RNGs), recording parallel sequences of random data at 65 sites around the world. A rigorous experiment tests the hypothesis that data from the RNG network will deviate from expectation during times of "global events," defined as transitory episodes of widespread mental and emotional reaction to major world events. An ongoing replication experiment measures correlations across the network during the designated events, and the result from over 345 formal hypothesis tests departs substantially from expectation. A composite statistic for the replication series rejects the null hypothesis by more than six standard deviations. Secondary analyses reveal evidence of a second, independent correlation, as well as temporal and spatial structure in the data associated with the events. Controls exclude conventional physical explanations or experimental error as the source of the measured deviations. The experimental design constrains interpretation of the results: they suggest that some aspect of human consciousness is involved as a source of the effects.     

浅谈医院药物临床试验质量控制体系的建设

目的 介绍本院执行《药物临床试验质量管理规范》（GCP）的工作经验,探讨医院药物临床试验质量控制体系的建设.方法 总结了药物临床试验在知情同意、试验的实施及实验室检查方面存在的问题.介绍了本院以GCP为指导原则,完善制度和标准操作规程、建立“三级质控”工作模式、强化GCP培训、加强机构内部的沟通协调、着力提升新药临床试验质量的具体做法和经验.结果与结论 新药必须在人体进行临床试验才能最终确定药物的有效性和安全性.医院药物临床试验机构建立完善的临床试验质量控制体系,有利于为公众筛选安全、有效的药物,推动医药卫生事业的进步与发展.     

Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen-dependent and independent prostate cancer cell lines

OBJECTIVE

To determine the benefit of genistein combined polysaccharide (GCP) in combination with the androgen receptor antagonist bicalutamide, the antimicrotubule taxane docetaxel, and the Src kinase inhibitor pp2 as part of a treatment regimen for advanced prostate cancer (CaP).

MATERIALS AND METHODS

The growth inhibitory and apoptotic effects of GCP in combination with bicalutamide, docetaxel and pp2 were evaluated in both the androgen‐dependent LNCaP line, and three androgen‐independent lines: CWR22Rv1, PC‐3, and LNCaP‐R273H. The LNCaP‐R273H model is an LNCaP variant expressing a p53^GOF allele; like CWR22Rv1 and PC‐3, it is able to grow in a minimal androgen environment. The effects of GCP treatment in combination with the aforementioned drugs were measured using an MTT assay, Western blotting, flow cytometric analysis, and caspase activation assay. Altered schedules of drug administration were explored using combinations of GCP and docetaxel.

RESULTS

GCP potentiated the activity of docetaxel in all four cell lines, resulting in growth inhibition and increased apoptosis. The combination of GCP and bicalutamide had enhanced activity in both the LNCaP and LNCaP‐R273H lines, which may better represent patient tumour cells after progression to androgen independence. Administration of docetaxel followed by GCP resulted in a synergistic interaction in LNCaP cells, with increased apoptosis. By contrast, GCP administered first showed subadditivity, probably resulting from GCP‐mediated induction of G1 arrest interfering with docetaxel activity.

CONCLUSION

These data suggest that GCP, an isoflavone‐enriched compound with minimal side‐effects and far superior intestinal absorption rate of genistein, has significant clinical potential in combination with docetaxel, bicalutamide or targeted agents for the treatment of advanced CaP.