用德尔菲法确定儿科阿奇霉素注射使用的快速建议指南的临床问题与结局指标

目的:旨在通过三轮德尔菲法,确定儿科阿奇霉素注射使用的快速建议指南中需纳入的临床问题与结局指标。方法:通过前期问卷调查、专家咨询并结合临床实践经验,指南指导委员会草拟了27个临床问题和12个结局指标。专家组在会上对其进行重要性评分,同时可进行补充。采用5分制对临床问题"是否有必要在指南中形成推荐意见"进行评分,1至5分重要性递增;采用9分制对结局指标进行评分,1至9分重要性递增。第一轮在会前采用网络投票形式进行,根据一定的共识规则,共识程度低的问题和指标将进入第二、三轮;第二轮在会中采用纸质问卷进行,投票分数在四分位数外和第一轮补充问题的专家填写意见说明;第三轮在会中采用网络投票形式进行,专家根据第二轮匿名反馈结果,对未形成共识和补充的问题与指标进行重新评分。统计分析专家组的基本信息和调查结果,并计算积极系数和协调系数。结果:共24位专家参与调查,专家组的遴选体现了多学科合作性、地域性和权威性。共有22个临床问题(包括适应证、用法用量、不良反应及护理和特殊人群用药)在指南中必须形成推荐意见或说明,5个临床问题需根据证据质量和专家共识决定是否形成推荐意见,形成7个关键结局和5个重要结局。第一轮与第三轮专家积极系数均为100%,且协调系数经第二轮匿名反馈后有所改善,专家的意见逐渐趋近一致。结论:本研究通过三轮德尔菲法问卷形成了儿科阿奇霉素注射使用的快速建议指南的临床问题与结局指标,为后续指南推荐意见的形成和制定打下了良好的基础。     

基于问卷调研法构建《口服组胺H1受体拮抗剂在儿童中合理应用的临床实践指南》的核心内容

目的：构建《口服组胺H₁受体拮抗剂在儿童中合理应用的临床实践指南》的疾病、药物、临床问题与结局指标，为同类指南核心内容的构建提供方法学参考与实践经验。方法：对指南专家组、医务人员与患者家属进行半开放式问卷调研，主要包括口服组胺H₁受体拮抗剂、儿童变态反应性疾病、临床问题与结局指标4个部分。采用Likert法（5分制或9分制）对每个部分进行定量评估，同时可进行定性补充。统计参与者的基本信息，根据评分结果和变异系数，纳入平均分不小于3.0分且变异系数不大于35%的内容，其余内容与补充内容则通过德尔菲法专家咨询法形成共识。采用Wilcoxon符号秩检验或Friedam检验对组间进行差异评估，对补充的问题进行描述性分析。结果：共回收242份有效问卷，包括指南专家组成员27份、医务人员163份和患者家属62份，参与调研者的各方面基本信息均有一定分布，代表性良好。指南拟纳入的疾病、药物、临床问题与结局指标在通过第一轮调研后纳入44条，专家组、医务人员和患者家属的大部分评估结果的差异不具有统计学意义（P<0.05），少数内容的差异体现在专家组与患者家属之间，患者家属评估分数更高。专家组通过两轮德尔菲法问卷，对10条未达成共识的内容和8条有效的补充内容进行了投票，拟纳入其中的10条。最终，指南确定了14种疾病、10个药物、11个临床问题和19个结局指标作为核心内容。结论：本研究采用了问卷调研法构建了指南的核心内容，以定量评估结合定性补充的方法，合理反馈了利益相关群体的意愿，为同类指南的核心内容构建提供了方法学参考和实践经验。     

基于德尔菲法确定霉酚酸治疗药物监测指南的临床问题与结局指标

目的:确定霉酚酸治疗药物监测指南的临床问题及结局指标。方法:应用德尔菲法向遴选专家进行3轮咨询,线上发放指南拟纳入临床问题及结局指标的调查问卷,采用Microsoft Excel 2016及SPSS Statistics 24软件整理、统计数据,通过计算积极系数、均数、满分频率、变异系数及协调系数进行质量控制。结果:共遴选31名专家,专业领域涵盖涉及使用霉酚酸类药物的多个学科,专家在投票过程中积极程度、集中程度及协调程度均具有较好的一致性,经过3轮德尔菲法投票后,最终确定了16个临床问题及5类结局指标,包括15个必须纳入指南的关键问题、1个重要问题。结论:通过德尔菲法构建的指南临床问题及结局指标具有一定的权威性及可信度,对霉酚酸治疗药物监测指南的后续制定具有重要指导意义。     

基于德尔菲法确定《心脏外科人血白蛋白合理使用快速建议指南》的临床问题及结局指标

摘要：目的:人血白蛋白广泛用于心脏外科围手术期患者的综合管理中,但国内外缺乏相关指南及共识,课题组严格遵循指南制定规范,制定《心脏外科人血白蛋白合理使用快速建议指南》,旨在促进人血白蛋白的合理使用。方法:项目专家组各位专家通过三轮德尔菲法完成本指南临床问题及结局指标的确定。结果:第一轮共有3个临床问题与14个结局指标达成共识,补充了6个临床问题与1个结局指标;第三轮有10个临床问题与1个结局指标进一步达成共识。最终共有13个临床问题在本指南中必须形成推荐意见或说明（纳入）,4个临床问题需根据证据质量与专家共识决定是否形成推荐意见（待定）,形成14个关键结局,1个重要结局。结论:本研究通过三轮德尔菲法调查确定了需要纳入《心脏外科人血白蛋白合理使用快速建议指南》的临床问题与结局指标,为指南的后续制定工作奠定了良好的基础。     

用德尔菲法确定伏立康唑个体化用药指南临床问题与结局指标

目的确定伏立康唑个体化用药指南需要纳入的临床问题与结局指标。方法用德尔菲法进行三轮专家咨询,并计算积极系数、协调系数和权威系数进行质量控制。结果共纳入18个临床问题和10个结局指标。其中,7个临床问题必须在指南中形成推荐意见,4个结局指标为关键结局。专家积极系数90.5%,权威系数均>0.75,仅有2个临床问题和2个结局指标协调系数≤15%。结论通过德尔菲法确定了伏立康唑个体化用药指南需要纳入的临床问题和结局指标,对指南的后续制定工作有重要指导意义。     

临床药学服务价值评价实践指南(第一版)

目的 为评价临床药学服务价值提供较为全面的评估体系,为改进和优化临床药学服务提供指导。方法 采用世界卫生组织(WHO)指南制定手册进行指南的研究设计。采用德尔菲法确定临床问题,通过系统检索,秘书组广泛收集相关问题已有的循证证据,完成系统评价、证据分级,撰写证据总结,由写作组根据秘书组的分析报告具体撰写指南。采用澳大利亚Jonana Briggs循证卫生保健中心(JBI)证据级别系统和WHO 2004年推荐分级的评估、制定与评价系统(GRADE)对该指南进行证据质量分级,通过德尔菲法对推荐意见及证据级别达成共识,最终形成《临床药学服务价值评价实践指南》(第一版)。结果 通过对100余位专家进行问卷调研,德尔菲法投票,该指南拟纳入临床药学价值评价指标23项。将纳入的指标相关内容按照纳入文献的人群、干预措施、对照和结局原则进行检索,并进行系统评价、Meta分析、网状Meta分析以及相关原始研究。每项检索策略经指南指导委员会审定,确定临床药学价值评价的推荐意见20项。结论 该指南提供了一套衡量临床药学服务质量和效益的指标体系,对于改进和提升医疗机构临床药学服务具有重要意义。     

《儿科阿奇霉素注射使用的快速建议指南》实施方案介绍

目的:规范和指导指南制订流程,保障科学和循证地完成《儿科阿奇霉素注射使用的快速建议指南》的制订。方法:介绍本指南实施方案,包括制订机构和指南注册,项目组的组建,指南适用范围,利益声明和资金资助,临床问题和结局指标的确定,循证证据的检索与处理,患者偏好和价值观调查,经济学分析,推荐意见的形成、外审和批准,指南发布、传播、更新等过程。结果:按本实施方案已完成指南指导委员会、专家组、秘书组的组建和指南的注册(注册号:IPGRP-2016CN013),形成了适应证、用法用量、不良反应及护理、特殊人群用药等临床问题以及有效性和安全性结局指标;并已于2017年末发布推荐意见,拟于2018年发表本指南全文及解读,计划于2022年对本指南进行更新。结论:本实施方案提供了方法学和纲要性的指导,可为科学和循证地制订指南提供依据,进而促进临床合理用药。     

阿奇霉素治疗社区获得性肺炎的观察

目的 观察阿奇霉素对社区获得性肺炎(CAP)的治疗效果.方法 因CAP住院患者30例,在应用头孢噻肟1500mg静脉滴注基础上口服阿奇霉素500mg/d;30例患者不加用阿奇霉素.分析患者的临床结局和住院时间.结果 接受阿奇霉素治疗患者住院时间显著缩短,病死率低,临床结局较好.结论 联合应用阿奇霉素治疗CAP可缩短住院时间,降低病死率,改善CAP患者预后.     

阿奇霉素联合痰热清治疗儿童肺炎支原体肺炎的临床观察

目的:分析并评估阿奇霉素+痰热清在儿童肺炎支原体肺炎治疗中的临床效果.方法:选取本院2015年9月～2017年3月80例儿童肺炎支原体肺炎患者,双盲法纳入实验组与对照组,实验组(n=40)给予阿奇霉素+痰热清,对照组(n=40)采用阿奇霉素,对比两组临床疗效.结果:实验组与对照组总有效率(95.0％VS72.5％)存在明显差异(P<0.05);实验组咳嗽、高热、肺部啰音改善时间均低于对照组(P<0.05);实验组不良反应发生率(5.0％)低于对照组(25％).结论:阿奇霉素联合痰热清治疗儿童肺炎支原体肺炎疗效显著.     

《肿瘤临床试验运用核心患者报告结局行业指南(草案)》解读

以患者为中心的药物研发理念愈发受到国内外研究者的重视,患者报告结局(patient-reported outcome, PRO)已逐渐成为临床试验的终点观察指标之一。PRO提供直接来自患者的健康信息,在医生的临床决策中起到重要作用。但肿瘤临床试验中PRO评估方法的运用和数据解释还有待改进。核心PRO指标的选用对PRO评估标准的一致性至关重要。2021年美国FDA发布的《肿瘤临床试验运用核心患者报告结局行业指南(草案)》针对肿瘤临床试验的药物研发,为申办方核心PRO收集、PRO评估工具选择和规范化试验设计提供指导意见。本文对该指南核心PRO的系统评估及运用进行解读,帮助新药临床试验从业者进一步了解PRO,对PRO在新药临床试验中的运用起到良好的促进作用。     

Comparison of the visual analog scale method and 5-point evaluation in student self-assessment of comprehension and acquisition in a model core curriculum for practical training

In examining assessment methods used for evaluating training, there have so far been no studies reporting any differences between the visual analogue scale (VAS) evaluation method, based on a rating scale, and evaluation methods based on an ordinal scale. Here we report the findings of an examination into differences and discrepancies between the results of the VAS method and a 5-point evaluation. Following the end of their training period, seven trainees carried out a self-evaluation regarding their level of understanding and performance using the 5-point evaluation and VAS methods. We then compared the average results of both assessment methods and examined the correlation between the two sets of figures. We found no differences between the 5-point evaluation method and VAS method in evaluating training for dispensing drugs, administering injections, pharmacy preparation, and medication management and instruction. There was also a significant correlation between average values for the 5-point evaluation and VAS method in evaluating training for dispensing drugs, administering injections, pharmacy preparation, and medication management and instruction. This led us to the conclusion that both the 5-point evaluation method and VAS method give similar results and outcomes in assessing the results of practical training.     

哮喘患者报告临床结局量表的研制和条目筛选

目的研制具有良好信度、效度与反应度,适用于新药临床试验或临床疗效评价的哮喘患者报告临床结局(PRO)量表。方法遵照美国食品药品管理局(FDA)PRO量表研制的程序化方法,建立量表的理论框架,建立条目池,并通过专家咨询、患者访谈等修改量表,得到含有72个条目的初量表。现场调查共收集108例样本,使用离散趋势法、因子分析法、相关系数法、克朗巴赫α系数法及修正条目的总相关系数法和项目反应理论5种方法对初量表进行条目筛选。结果经过条目筛选,调整量表的框架结构,共保留67个条目,分为生理、心理、社会、治疗4个领域及13个方面。结论哮喘PRO量表严格按照国际量表的操作原则和方法进行,科学性强、结论可信,有利于临床研究中推广使用。     

Use of online opioid overdose prevention training for first-year medical students: A comparative analysis of online versus in-person training

Purpose: In response to the opioid epidemic and efforts to expand substance use education in medical school, the authors introduced opioid overdose prevention training (OOPT) with naloxone for all first-year medical students (MS1s) as an adjunct to required basic life support training (BLST). The authors previously demonstrated improved knowledge and preparedness following in-person OOPT with BLST; however, it remains unclear whether online-administered OOPT would produce comparable results. In this study, the authors perform a retrospective comparison of online-administered OOPT with in-person-administered OOPT. Objectives: To compare the educational outcomes: knowledge, preparedness, and attitudes, for online versus in-person OOPT. Methods: In-person OOPT was administered in 2014 and 2015 during BLST, whereas online OOPT was administered in 2016 during BLST pre-work. MS1s completed pre- and post-training tests covering 3 measures: knowledge (11-point scale), attitudes (66-point scale), and preparedness (60-point scale) to respond to an opioid overdose. Online scores from 2016 and in-person scores from 2015 were compared across all 3 measures using analysis of covariance (ANCOVA) methods. Results: After controlling for pre-test scores, there were statistical, but no meaningful, differences across all measures for in-person- and online-administered training. The estimated differences were knowledge: ?0.05 (0.5%) points (95% confidence interval [CI]: ?0.47, 0.36); attitudes: 0.65 (1.0%) points (95% CI: ?0.22, 1.51); and preparedness: 2.16 (3.6%) points (95% CI: 1.04, 3.28). Conclusions: The educational outcomes of online-administered OOPT compared with in-person-administered OOPT were not meaningfully different. These results support the use of online-administered OOPT. As our study was retrospective, based on data collected over multiple years, further investigation is needed in a randomized controlled setting, to better understand the educational differences of in-person and online training. Further expanding OOPT to populations beyond medical students would further improve generalizability.     

The validity and reliability of the global index of safety (GIS)

OBJECTIVE: The global index of safety (GIS) is an adverse event (AE) based instrument designed to evaluate the safety profile of drugs. This paper presents the evaluation of the inter-rater reliability and validity of a 94-item GIS for antipsychotics through Rasch analysis. RESEARCH DESIGN AND METHODS: A total of 194 psychiatrists participating in an outpatient pharmacoepidemiologic study of olanzapine in schizophrenia rated the severity that each AE would have on a 5-point scale. Reliability was determined through a paired comparison design involving the new independent ratings of 101 different psychiatrists participating in another study of olanzapine in acute inpatient units. Spearman's, Pearson's and Intra-class correlation (ICC) coefficients were used to estimate the inter-rater reliability of the AE weights. Validity was analyzed through the Rasch rating scale model. RESULTS: Reliability coefficient estimates were excellent (Spearman = 0.99, Pearson = 0.99, ICC = 0.98), supporting the inter-rater reliability of the item weights. Through goodness-of-fit statistics and the investigation of the hierarchy of item calibrations, Rasch analysis confirmed the validity of the instrument. CONCLUSION: The data presented here on inter-rater reliability estimates of adverse events related to antipsychotic drugs indicate that GIS is a promising alternative for the evaluation of the safety profile of drugs.     

符合中医药特点的中药新药评价思路探讨

目的：探讨中药新药区别于化学药新药的评价思路。方法：以真实世界证据为工具,以整体证据评价为方法,以电子化的患者报告结局为技术支持,创新中药新药评价思路。结果：1)提出中药新药质量控制中的质量一致性评价思路。在单一角度对中药新药质量一致性无法评价的前提下,采用整体证据方法这种多角度的审评观念,用真实世界证据评价多批次药品的疗效一致性,适当放宽中药新药质量一致性的要求,使中药新药的疗效一致性评价作为质量一致性评价的有力补充。2)提出中药新药临床疗效评价思路。在传统临床试验的评价基础上,以患者为中心进行临床试验设计,创建电子化的患者报告结局,关注患者生活质量改善,形成临床疗效的支持性证据。结论：鼓励采用新工具、新方法、新技术、新思路,在中药新药评价中充分体现中药临床疗效评价方法的开创性,创新中药新药评价思路。     

On evaluation of consistency in multi-regional clinical trials

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population). The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, time points of assessment, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. However, the challenge is there is no detailed guidance on the definition of ‘consistency’ and methodology to evaluate it. Therefore, the questions are: how to evaluate consistency and what statistical methods are appropriate to be used for consistency evaluation? In this article, several statistical tests for consistency (similarity) between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation in this article through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given. Other aspects that should be considered for consistency evaluation are also provided.     

Randomized versus nonrandomized studies of alcohol treatment: participants,methodological features and posttreatment functioning

OBJECTIVE: Randomized trials are widely acknowledged to be the most rigorous method to estimate the comparative efficacy of treatments. Concerns have been raised, however, about the generalizability of findings from randomized trials of alcohol treatments to actual treatment circumstances, and about the internal validity of randomized trials. The purpose of this review was to compare the participants, methodological features and posttreatment functioning in randomized and nonrandomized studies of alcohol treatment. METHOD: Using systematic literature search techniques, 232 randomized and 92 nonrandomized trials published between 1970 and 1998 were identified. Each investigation was scored on a methodological quality scale, participant characteristics were recorded and participants' follow-up abstinence and improvement rates were calculated. RESULTS: Randomized investigations were more likely to use participant selection criteria, to use recognized diagnostic criteria to characterize participants and to stringently implement treatment and assess outcomes. Nonrandomized investigations were more likely to assess outcomes in higher proportions of participants over longer follow-up periods and to have greater statistical power t o detect treatment effects. Abstinence and improvementrates following active treatment were similar for the two types of design (proportion abstinent: 0.35 and 0.39, and proportion improved: 0.52 and 0.54, for randomized and nonrandomized trials, respectively), even when differences in study features were controlled. CONCLUSIONS: The contrasting strengths and weaknesses of randomized and nonrandomized studies suggest that they should be considered as complementary forms of treatment evaluation, in the alcohol treatment field and perhaps more generally.