Recent advances in medicines for children and neonates

The European Society for Developmental, Perinatal and Paediatric Pharmacology held its 13th Biennial Congress in Oslo, Norway. The congress was attended by over 100 health professionals from all around the world. The focus of the congress was recent advances in drug therapy in neonates and children. Alongside invited speakers, there were a host of presentations by young investigators which consisted of oral and poster presentations.     

Public awareness and views on unlicensed use of medicines in children

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children.
• There is little published information on the views of the public on this important area of paediatric care.

WHAT THIS STUDY ADDS

• A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known.
• However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children.
• Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life-threatening illness.

AIMS

To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials.

METHODS

Members of the public completed a questionnaire survey administered by face-to-face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children.

RESULTS

One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P < 0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P < 0.05) i.e. a child in good health (3.9%) vs a child with a life-threatening condition (41.9%).

CONCLUSIONS

There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life-threatening condition.     

Clinical trials of chemotherapy for falciparum malaria

Plasmodium falciparum remains one of the World’s most prevalent and devastating pathogens. Mainly for economic reasons, the parasite’s ability to develop resistance to drugs has not been matched by the rate at which new compounds are developed. Even so, there are new drugs (or new combinations of old drugs) currently under investigation, or in the process of development (at the moment):     

The development and assessment of biological treatments for children

The development of biological agents with specific immunological targets has revolutionized the treatment of a wide variety of paediatric diseases where traditional immunosuppressive agents have been partly ineffective or intolerable. The increasing requirement for pharmaceutical companies to undertake paediatric studies has provided impetus for studies of biologics in children. The assessment of biological agents in children to date has largely relied upon randomized controlled trials using a withdrawal design, rather than a parallel study design. This approach has been largely used due to ethical concerns, including use of placebo treatments in children with active chronic disease, and justified on the basis that treatments have usually already undergone robust assessment in related adult conditions. However, this study design limits the reliability of the data and can confuse the interpretation of safety results. Careful ongoing monitoring of safety and efficacy in real-world practice through national and international biologics registries and robust reporting systems is crucial. The most commonly used biological agents in children target tumour necrosis factor-α, interleukin-1, interleukin-6 and cytotoxic lymphocyte-associated antigen-4. These agents are most frequently used in paediatric rheumatic diseases. This review discusses the development and assessment of biologics within paediatric rheumatology with reference to the lessons learned from use in other subspecialties.     

小儿积滞中药临床试验设计与评价技术指南

目的 以“肠-关节”轴为切入点,探讨金藤清痹颗粒抗类风湿关节炎的作用机制。方法 按体质量将大鼠随机分为6组,即对照组、模型组、双氯芬酸钠组以及金藤清痹颗粒高、中、低剂量组,每组6只。采用胶原诱导法进行造模,设计金藤清痹颗粒高、中、低剂量组给药剂量分别为6.30、3.15、1.58 g/kg;双氯芬酸钠组给药剂量为3 mg/kg;对照组和模型组ig等量生理盐水,给药4周。苏木精-伊红染色法（HE）观察大鼠踝关节部位病理变化,酶联免疫吸附测定法（ELISA）检测大鼠血清相关炎症指标,16S rDNA分析盲肠内容物中肠道菌群变化。结果 与模型组比较,金藤清痹颗粒可明显降低胶原诱导型关节炎模型大鼠关节肿胀度,减少踝关节炎性细胞浸润,同时可显著降低胶原诱导型关节炎大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、C反应蛋白（CRP）水平（P＜0.05、0.01）;16S rDNA结果显示,金藤清痹颗粒6.30 g/kg可增加Cyanobacteria、软壁菌门、疣微菌门、梭杆菌门、毛螺菌科NK4A136群和Ruminiclostridium 5等菌群的相对丰度,以及降低变形菌门、乳杆菌属和瘤胃球菌属1等菌群的相对丰度。结论 金藤清痹颗粒可能通过调控“肠-关节”轴发挥抗类风湿关节炎的作用。     

小儿支原体肺炎的临床诊断与治疗

目的　总结小儿支原体肺炎的临床诊断与治疗现状。方法　检索国内有关文献。结果　小儿支原体肺炎的临床诊断标准有三个方面 :①临床症状体征的具体表现 ;②胸部X光线检查 ;③实验室检查项目 :血清冷凝集试验 ;血清肺炎支原体抗体测定 (主要检测IgM) ;聚合酶链反应方法 (PCR Mp DNA)检测肺炎支原体。药物治疗均采用大环内酯类抗菌药物。结论　小儿支原体肺炎的临床诊断除常规检查项目 ,血清学检查已成为必要而确切的标准。红霉素因疗效肯定 ,价格低廉仍作为首选药物。但红霉素药物不良反应发生率高 ,特别是引起胃肠道反应较多 ,患者耐受性差。阿奇霉素以其优良的体内药物动力学特点 ,优良的临床疗效 ,不良反应发生率最低等优势 ,可作为治疗小儿支原体肺炎的较佳选择。但因价格较贵 ,仍不能广泛应用于临床治疗。     

新药临床试验中医学伦理学问题的探讨

目的通过对新药临床试验中存在的医学伦理学问题的探讨,阐明在新药临床试验研究过程中,如何解决好试验阶段相关的医学伦理学问题。方法以相关的法律、法规、原则、规范以及社会伦理、道德为依据,探讨新药临床试验中的医学伦理学问题。结果临床受试者是一群生理甚至于心理均处于非正常状态的病人,因此在新药临床试验研究过程中,不但涉及到大量的技术问题,更重要的是存在相关的医学伦理学问题。结论在新药临床试验研究过程中,试验者必须执行和遵守相关的法律法规,解决好试验阶段相关的医学伦理学问题。     

家长对儿童药物临床试验认知与态度调查

目的:了解家长对儿童药物临床试验的认识和态度,为开展儿童药物临床试验提供参考。方法:选择2017 年1-8 月在上海交通大学医学院附属新华医院、复旦大学附属儿科医院、上海交通大学附属儿童医院、哈尔滨儿童医院住院患儿家长,自愿参加问卷调查,收集有效问卷468 份。重点调查内容为儿童药物临床试验目的、意义、必要性、现状以及家长顾虑等。结果:9.4%的家长了解儿童药物临床试验目的,不同学历家长的认识差异有统计学意义(P<0.05);71.6% 的家长认为儿童用药缺乏依据,66.2%家长认为有必要开展药物临床试验,不同学历家长的认识差异有统计学意义(P<0.05);17.9% 的家长认为临床试验管理比较规范,不同学历家长的认识差异无统计学意义(P>0.05);不需要及不知道药物临床试验需要医院伦理委员会审查的家长小学学历占比最高,分别为13.6% 和50.0%,不同学历家长对医院伦理委员会审查的认知差异有统计学意义( P<0.05);担忧孩子身体受伤害的家长占78.8%,担心药物副作用大的家长占69.0%,不同学历的家长对这两方面的认识差异均有统计学意义(P<0.05)。结论:大部分家长对儿童药物临床试验的认识存在偏差,针对不同学历的家长通过加强宣传、沟通,提高家长对儿童药物临床试验的正确认识,是顺利开展儿童药物临床试验的前提条件。     

药物临床试验质量控制的若干思考及实践

目的：探讨当前药物临床试验质量管理中存在的问题及应对策略。方法：分析在药物临床试验质量保证中存在的问题,并结合实际情况提出解决办法。结果：上海中医药大学附属曙光医院结合实际情况采取各种举措,使临床试验质量得到提高。结论：药物临床试验质量的提高需要申办者、研究者及药物临床试验机构各方共同努力。     

儿科中成药的临床有效性探索

儿科中成药的临床有效性探索主要在新药的Ⅱ期临床试验中执行.由于历史原因,目前已经上市的儿科中成药品种大多未进行过临床试验,其上市后临床再评价一般也可将有效性探索作为研究目的.阐述了儿科中成药有效性探索的内容,尤其是量效关系探索的设计与统计方法,同时总结了儿科中成药有效性探索的特点并提出可行性建议.     

Reporting adverse events in randomized controlled trials

PURPOSE: How randomized controlled trial results are reported may minimize concerns and detection of adverse side effects. We aimed to describe the methods of reporting adverse events in these published trials. METHODS: Five frequently cited journals were investigated: Annals of Internal Medicine, British Medical Journal, JAMA, The Lancet, and the New England Journal of Medicine. For each journal, all randomized controlled trials conducted on the use of a medication were selected from January 2000 through June 2003. All issues of each journal were reviewed manually. Information retrieved included any mention of adverse events in the abstract, methods, results, or discussion section of the article; or inclusion of adverse events data in tables or figures. We also cataloged whether there was a separate subheading in the results section for reporting adverse events. Reports of trials that referred to methods described in a previous report were excluded. RESULTS: There were 521 eligible articles. Explicit mention of adverse events was in 328 (63%) of abstracts (range 47-66%), 380 (73%) of methods (range 51-81%), 464 (89%) of results (range 80-95%), and 250 (48%) of tables (range 31-49%). There was a separate subheading for adverse events in 240 (46%) (range 22-64%) of the eligible articles. CONCLUSION: There is variation among authors and journals as to the location of reporting adverse events and the means by which it is done. Authors and editors should include specific information on adverse events when reporting the results of randomized controlled trials. It would be ideal if there was more consistency among authors and journals as to how these adverse events are described.     

我国儿科药物临床试验数据分析及启示

目的:研究我国儿科药物临床试验登记现状,为促进儿科药品研发提供建议与参考.方法:收集国家药品监督管理局药品审评中心(CDE)药物临床试验登记与信息公示平台中儿科药物公示信息,对试验类型、试验分期、受试者招募、保险、临床试验数据监察委员会(DMC)等信息采用比率法进行统计分析.结果与结论:截至2020年6月份,平台共登记...     

某院药物临床试验不良事件监控质量调查

目的:分析及评价某院药物临床试验不良事件监控质量.方法:对照不良事件监控的质量评分标准,调查2007-2013年结题的Ⅱ~Ⅲ期项目中不良事件监控的质量得分及各要素的年均得分率.并对2007-2013年发生的15例严重不良事件(SAE)监控情况进行分析.结果:总体上,某院药物临床试验不良事件监控质量得分及各要素得分率均呈现逐年增长的趋势.2011年某院针对不良事件的监控实施展开全面整改工作,整改前存在的问题主要集中在:启动会培训缺失或不完整、实验检查类不良事件收集的遗漏、SAE获知的滞后性、SAE报告表原件的遗失、不良事件源文件记录的缺失或不完整.通过完善规章制度、建立应急预案、强化伦理审查力度、强化试验前不良事件的预防措施、加强机构办公室及科室的监控力度等措施,某院不良事件的监控质量显著提高.结论:加强临床试验机构对不良事件的监控作用,依靠临床试验各部门的共同努力,不断完善安全性监控体系,才能提高临床试验的质量和水平.     

A prospective study of adverse drug reactions in hospitalized children

AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.     

基于文献分析法的药物临床试验信息化建设

目的:梳理药物临床试验信息化建设研究脉络,了解并掌握药物临床试验信息化建设研究热点和发展趋势。方法:本研究采用知识图谱CiteSpaceⅤ软件,在2000年至2020年中国知网数据库391条文献的基础上,从文献数量分析、研究机构分析、作者分析、研究热点主题以及研究趋势分析等角度进行了深入探讨,并绘制知识图谱,梳理药物临床试验信息化建设研究脉络。结果:分析表明近20年来药物临床信息化建设相关研究论文发表数量波动上升,主要研究机构在该领域大都有较强的研究能力,但研究机构间的联系还较为松散,学者间的学术交流还有待加强。在热点研究上的转变体现了该领域更加注重系统化和保护受试者权益。结论:药物临床试验信息化建设研究热点主要集中于临床试验、药物临床试验、质量控制等方面。通过信息化建设进一步提高试验管理效能,保证药物临床试验可靠规范,有效降低药物临床试验风险隐患是未来研究趋势。