Use of Alternative Designs and Data Sources for Pediatric Trials

Abstract

Children are considered a vulnerable group and as such are granted additional protection as research subjects. Research projects using children as research subjects are justifiable if the answer to the scientific question of the study cannot be obtained by enrolling adult subjects (cf. scientific necessity). Thus, there is an ethical obligation to explore innovative analytical strategies that seek balance between the feasibility of conducting a trial and maximizing the utilization of data on efficacy and safety. On this note, there is enthusiasm for implementing some less popular but efficient alternative designs for confirmatory pediatric trials. Within the pediatric extrapolation paradigm, examples of such designs, other than purely based on pharmacokinetic/pharmacodynamic data, are described in this article along with their advantages and disadvantages. This article will also discuss how to incorporate alternative data sources in the analysis of pediatric clinical trials. A discussion of existing approaches and a road-map to their utilization will be provided. Real case examples on the use of the approaches are provided.     

Five-year change scores in old age for six neuropsychological tests and normative data for the Useful Field of View (UFOV) test: The influence of physical health

Introduction: Neuropsychological assessment of cognitive change over time is often conducted in clinical settings, but whether neuropsychological change scores are influenced by physical health has, as far as we know, not been examined previously.

Method: In a sample of 153 older Swedish adults (age range, 72–86 years), we evaluated the influence of common age-related diseases, terminal decline pathology, age, education, and gender, to provide (a) preliminary test-specific regression weights and 90% confidence intervals to assess significant change in performance after five years on tests of visual scanning, mental shifting, visual spatial ability, memory, reaction time, and selective attention, and (b) normative data for the Useful Field of View test (UFOV) from a single testing occasion.

Results: Multiple regression analyses showed that test–retest changes were affected by physical health for mental shifting, visual spatial ability, memory, and reaction time, by age for mental shifting and visual reaction time, by education for visual spatial ability, and by Age × Education for auditory reaction time. Gender did not affect any of the change scores. The overall average of variance explained was 2.5%: up to 8.1% for physical health, 4.4% for age, and 3.6% for education. The UFOV scores were mostly influenced by age, but also by physical health and education.

Conclusions: The findings indicate that considering the influence of health on normative change scores in old age in addition to demographic factors leads to more accurate predictions of whether true change has occurred.     

呋塞米注射液在新生儿湿肺中的应用

目的观察呋塞米注射液在新生儿湿肺中的疗效。方法选取2018年1月—2019年12月医院新生儿科收治的新生儿湿肺70例,随机分为试验组35例和对照组35例,二组性别、胎龄、出生体质量、生产方式的差异无统计学意义(P>0.05),试验组在对照组常规治疗的同时加用静注呋塞米注射液0.5 mg/(kg·d),疗程3 d,比较两组平均住院时间、停氧时间、48小时内症状缓解例数。结果平均住院时间:试验组(5.00±1.31)d,对照组(6.06±1.75)d;总用氧时间:试验组(49.04±18.23)h,对照组(63.80±24.11)h;48 h内呼吸症状改善者:试验组24例(68.57%),对照组15例(42.86%),二组比较在平均住院时间、总用氧时间及48小时内症状缓解例数,差异均有统计学意义(P<0.05)。结论呋塞米注射液治疗新生儿湿肺在平均住院时间、总用氧时间和48小时内呼吸症状缓解优于对照组,有一定的疗效。     

多媒体联合情景教学在急诊医师培训中的应用

目的探讨多媒体联合情景教学在急诊医师培训的应用效果。方法将本院2018年1月-2018年12月的34名急诊医师纳入观察组,应用多媒体联合情景教学法对其进行院内培训,另将本院2017年1月-2017年12月的34名急诊医师纳入对照组,应用传统教学法对其进行培训,对比两组医师的考试成绩、岗位胜任能力以及应急能力。结果观察组理论知识与技术操作的考试成绩均高于对照组,观察组自学、交流、表达、理解、解决问题的能力以及综合能力的评分均高于对照组,观察组急救意识、急救效率、病情评估、团队合作、职业防护的评分均高于对照组(P<0.05)。结论多媒体联合情景教学在急诊医师培训的应用效果显著,可明显提高医师的考试成绩、岗位胜任能力以及应急能力。     

中西医结合治疗慢性支气管炎急性发作临床观察

目的研究中西医结合治疗慢性支气管炎急性发作的效果。方法选取2018年11月-2019年11月就诊的60例慢性支气管炎急性发作期患者作为此次研究的对象,其中2018年11月-2019年4月到院的30例患者归为对照组,予以常规西医给药治疗;2019年4月-2019年11月到院的30例患者归为观察组,在对照组的基础身上予以清化止咳汤治疗,对比2组的临床疗效、不良症状改善的时间变化情况及不良反应的发生情况。结果观察组患者的临床总有效率(93.33%)显著高于对照组(73.33%)(P<0.05)。观察组患者不良症状改善的时间均短于对照组(P<0.05)。观察组患者的不良反应发生率(6.67%)显著低于对照组(26.67%)(P<0.05)。结论予以慢性支气管炎急性发作期患者中西结合治疗,能够有效的减轻其临床症状,使不良症状能够更快速的得到改善,并且减少不良反应的发生现象,进一步提高患者身体健康的恢复。     

加味黄芪建中汤治疗脾阳虚型胃肠功能紊乱临床研究

目的:观察加味黄芪建中汤治疗脾阳虚型功能性胃肠功能紊乱的临床疗效。方法:将患者随机分成2组,对照组用枸橼酸莫沙比利治疗,治疗组运用枸橼酸莫沙比利治疗的基础上加用加味黄芪建中汤治疗,均治疗共4疗程。观察临床疗效及中医症状评分情况。结果:对照组有5例患者失访,疗效结束后显效率治疗组36.0%,对照组20.0%,2组比较,差异有统计学意义(P<0.05);治疗后2组胃脘痞满、食欲减退、神疲乏力评分与治疗前比较,差异有统计学意义(P<0.05),2组胃脘痞满、食欲减退以及神疲乏力等评分分别比较,差异均有统计学意义(P<0.01)。结论:加味黄芪建中汤能改善脾阳虚型胃肠功能紊乱的症状,有良好的临床疗效,优于单纯使用枸橼酸莫沙必利治疗。