药物临床试验记录文件中常见问题及规范实施办法探讨

目的:总结临床试验记录文件中常见的问题,提出规范的文件记录做法,为提高药物临床试验数据记录质量提供参考。方法:参照药物临床试验质量管理规范,结合作者从事药物临床试验质量控制工作的经验,对实际工作中发现的临床试验记录文件中存在的问题进行分析,并探讨符合药物临床试验规范的文件记录做法和相关措施建议。结果:研究者和监察员的综合素质是影响药物临床试验记录文件质量的主要原因。结论:加强对研究者和监察员的试验资质考察、GCP和SOP培训,对临床试验进行项目组、专业组和机构办公室三级质量控制监管,引入国外SMO管理模式、聘请CRC,建立药物临床数据信息化系统是提高药物临床试验记录文件质量的办法。     

《药物临床试验质量管理规范》在疫苗临床试验中的应用

目的说明在疫苗临床试验中严格执行《药物临床试验质量管理规范》(GCP)的重要意义。方法对临床试验过程中发现的问题依据GCP进行分析,探讨解决办法,说明疫苗临床试验严格执行GCP的必要性。结果疫苗临床试验中不遵循GCP的行为是导致临床试验不能顺利开展甚至失败的重要原因。结论 GCP是适用于疫苗临床试验的规范文件,严格遵循GCP和相关法规是保证临床试验数据和结果的质量及科学性、准确性、可靠性和完整性的关键。     

Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy

Ethnopharmacological relevance

PHY906, is a decoction of a mixture of the four herbs Scutellaria baicalensis Geori, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. A combination of these four herbs has been in continuous use in traditional Chinese medicine for over 1800 years for treating a variety of gastrointestinal distress such as diarrhea, cramps, nausea, vomiting etc.

Aim of the study

Preclinical and clinical studies to find PHY906 enhances the therapeutic indices of a broad spectrum of anticancer agents.

Materials and methods

Using various mouse tumor xenograft and allograft models, PHY906 has been shown to enhance the chemotherapeutic efficacy of a variety of anticancer agents in various cancers. The PHY906 clinical program consists of five trials in three different types of cancers in both the United States and Taiwan. To date, approximately 150 subjects have received PHY906 in combination with chemotherapy in these five clinical studies.

Results

Preclinical studies have shown that PHY906 enhances the therapeutic indices of a broad spectrum of anticancer agents. These findings have been examined in clinical studies for colorectal, liver, and pancreatic cancers when PHY906 is used as an adjuvant to chemotherapy and the results were promising; i.e. PHY906 could reduce chemotherapy-induced toxicities and/or increase chemotherapeutic efficacy. Furthermore, PHY906 did not affect the pharmacokinetics of the chemotherapeutic agents used. Some information has been obtained regarding the mechanism of action of PHY906 in preclinical studies. A comprehensive platform, PhytomicsQC that integrates chemical and biological fingerprints together with a novel biostatistical methodology has been developed to assess the quality of different batches of PHY906.

Conclusions

Over a ten-year period, the multiplex technology “PhytomicsQC” has been used to show batch-to-batch consistency of PHY906 production. Advanced clinical trials are ongoing to demonstrate the effectiveness of PHY906 as adjuvant therapy for cancer patients undergoing chemotherapy.     

GCP与临床试验质量管理

通过研究天津市传染病医院在药物临床试验工作中具体实施《药物临床试验质量管理规范》(Good Clinical Practice,GCP)的实际情况,探讨如何提高临床试验质量的具体措施.药品的安全、有效关乎人民的生命健康,因此药物临床试验的科学性与真实性绝对不容质疑.做好药物临床试验工作必须保证试验质量,医院必须高度重视药物临床试验机构的发展,紧紧把握工作重点,按照GCP及相关法律法规要求开展工作,建立完善且行之有效的管理体制,规范试验流程,加强对医护人员的GCP培训及科研队伍建设,不断增强管理意识、提高药物临床试验质量.     

Evaluation of safety and tolerance of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation: A randomized,placebo-controlled,double-blind study

Probiotic organisms have shown promise in treating diseases. Previously, we have reported on the efficacy of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation at lowering serum cholesterol levels in otherwise healthy hypercholesterolemic adults. This study investigates the safety and toxicology of oral ingestion of microencapsulated L. reuteri NCIMB 30242 in a yogurt formulation. A randomized group of 120 subjects received a dose of 5 × 10¹⁰ CFU microencapsulated L. reuteri NCIMB 30242 in yogurt (n = 59) or placebo yogurt (n = 61) twice/day for 6 weeks. Clinical chemistry and hematological parameters of safety were analyzed. Fecal samples were collected at these time points for the analysis of deconjugated bile acids. The frequency, duration and intensity of adverse events (AEs) and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic yogurt and placebo yogurt treated groups were detected in either the blood clinical chemistry or hematology results and there was no significant increase in fecal deconjugated bile acids (P > 0.05) between treated and control groups. The frequency and intensity of AEs was similar in the two groups. These results demonstrate the safe use of this formulation in food.     

欧洲药品局对在第三国进行临床试验的伦理和GCP问题的考虑

众所周知,欧洲药品管理局(EMA)是欧盟的一个非集权实体,主要职责是通过审评和监督人用药品和兽用药品保护并促进公众和动物健康。欧洲药品管理局负责对药品的欧洲上市许可申请(集中程序)进行技术审评。对来源于欧盟以外的临床研究数据,如何保证受试者的合法权益,保证临床研究符合伦理和GCP的要求,成为欧洲药品局关注的一个问题。2009年,EMA起草了"对在第三国进行的人用药品临床试验中以及向欧洲药品管理局递交的上市许可申请中的伦理和GCP草案"并广泛征求意见,2010年9月在伦敦召开会议对草案进行了讨论。本文主要介绍该草案的基本情况以及会议讨论要点。     

关于中医特色GCP的思考

我国《药品临床试验管理规范》（ＧＣＰ）的颁布施行,将对于中药临床试验循着科学化、规范化方向发展起到巨大的推动作用。同时也是新形势对中医药发展提出的新要求。努力探索一套既体现中医药特色,又与国际标准接轨的ＧＣＰ规范操作系统,构筑规范的中医证候诊断标准和临床结局评估标准,不仅是中医药现代化发展的需要,也是对现行ＧＣＰ的一种有益的补充。     

Safety and pharmacokinetics of Alpha-1 MP (Prolastin®-C) in Japanese patients with alpha1-antitrypsin (AAT) deficiency

Background

Alpha₁-Proteinase Inhibitor, Modified Process (Alpha-1 MP) is used for augmentation therapy in alpha1-antitrypsin deficiency (AATD), an extremely rare disease in Japan. Weekly doses of 60?mg/kg Alpha-1 MP have been shown to be safe and well tolerated in non-Japanese subjects, but the safety and pharmacokinetics (PK) have not been evaluated in Japanese subjects. The objectives of this study were to evaluate the safety and PK of 60?mg/kg Alpha-1 MP administered by weekly IV infusions over 8 weeks in Japanese subjects with AATD.

浅谈GCP培训在本科护士科研能力培养中的作用

科研能力的培养是国家教育部对本科护士的教育目标之一.在临床实践中,如何培养及充分发挥本科护士的科研能力一直是临床带教中的重要问题.文章浅谈本科护士经过药物临床试验质量管理规范（good clinical practice,GCP）培训后,对其科研能力的培养.     

Single priming dose of meningococcal group C conjugate vaccine (NeisVac-C) in infants

Since the introduction of the meningococcal C conjugate (MCC) vaccine in the pediatric population in 1999, numerous clinical studies have confirmed the immunogenicity and safety of the NeisVac-C^® vaccine, and several have observed a strong immune response after a single priming dose, which could be successfully boosted. Maximizing protection of infants with as few vaccine doses as possible would increase the general acceptability of the immunization strategies and support broader coverage without increasing vaccination costs.