团体标准在药品标准工作中的作用与展望

目的：分析团体标准在药品标准工作中的作用,提出药品标准领域内发展团体标准的建议。方法：对团体标准概念和法律地位进行深入分析,对国内外团体标准发展现状进行总结。结果：药品领域内发展团体标准具有积极意义,可培育完善的标准体系,提高企业竞争力,促进国家药品标准工作的发展。结论：药品标准领域内推动团体标准工作非常重要,但必须加强引导,确保团体标准和国家标准协调发展。     

新生儿用药分剂量操作及其国际管理现状

新生儿作为儿科的特殊人群，其生理特点决定其药动学、药效学与成人存在很大不同，用药剂量变异性大，具有胎龄、体质量依赖性等特点。目前很多剂型不适用于新生儿治疗，一般通过对儿童或成人制剂分剂量操作、临时配制液体制剂等方法来改善，但分剂量操作存在辅料的安全性，复配溶液的稳定性、有效性等问题。本文主要对国内外新生儿用药分剂量操作现状及相关的操作规范和标准进行概述，旨在为国内新生儿分剂量操作提供参照，提高国内新生儿用药的安全性和可及性。     

国家药品标准与生产假药罪的刑法适用标准分析

药品标准是生产药品的准绳,我国《药品管理法》规定,药品所含成份与国家药品标准规定成份不符的,是假药.《刑法》对生产假药行为的刑法规制,是以《药品管理法》对假药认定适用为根据.从严格意义上说,生产药品所执行的标准不仅是国家药品标准一种标准形式,药品标准还有药品注册标准、地方药品标准(如中药饮片规范等),对未依据国家药品标准生产的药品是否假药的判断,不能适用国家药品标准认定,对生产假药行为的刑法规制认定适用标准存在有缺失空间.本文分析认为,国家药品标准需要有狭义和广义二元之分,狭义即严格法定意义,是《药品管理法》规定的含义;广义的概念包括狭义内容和药品注册标准、地方标准.通过有权解释,完善广义的国家药品标准内容,能够解决对生产假药行为刑法规制适用标准的问题.     

口服固体制剂精准分剂量在精准用药中的探索与实践

目的:为医院口服固体制剂的使用提供一种精准分剂量方法,为临床合理用药提供参考。方法:利用药片切割器、药片磨粉器等对口服固体制剂进行分劈、磨粉或胶囊内容物直接分装,并称重进行调整,以保证分剂量准确度控制在均分量的85%~115%以内。结果:提供药品精准分剂量服务,能够保证分剂量准确度,提高用药安全性、有效性和方便性,减少药品浪费,降低用药成本。结论:医院药学部门开展药品精准分剂量是精准用药的现实基础,使医院药学服务更加精细,提高患者用药依从性,医护患满意,值得推广。     

药品质量管理及控制标准制订与解析

药品质量管理及控制是医疗机构药事管理的重要内容,加强医疗机构药品质量管理及控制有助于提升医疗质量,从而为患者的用药安全提供有力的保障。为实施同质化的药品质量管理及控制,编制团队以科学性、通用性、指导性和可操作性为编写原则,通过梳理问题、征集意见、专家论证审议,最终形成国内首部对药品质量管理及控制全过程进行规范的团体标准。该文阐述药品质量管理及控制标准制订过程,并对标准内容进行解析,以期为各级各类医疗机构开展药品质量管理及控制提供建议和指导。     

《药品标准管理办法》解读与思考

2023年7月,国家药品监督管理局发布《药品标准管理办法》（以下简称《办法》）。本文就《办法》的主要内容进行解读,分析其存在的不足为：《办法》现有条文中对药品标准代号和药品标准信息化建设目标未明确。建议国家药品监督管理部门及时向标准化主管部门申请药品标准代号“YB”字母的确权,并将药品标准代号、编号规则在下一轮《办法》修正时写入条文,同时明确药品标准信息化体系建设目标;按用户界面层、计算处理层、数据存储层的基本框架搭建国家药品标准数据共享平台,免费向社会公开数字化药品标准,提供查阅和下载服务。     

我国儿科药品分剂量工作现状及思考

缺乏儿童适宜剂型和规格的药品是目前儿科治疗面临的主要问题之一,由此导致药品分剂量在儿科临床治疗中极为普遍。由于缺少相应的政策支持和指南规范,我国儿科药品分剂量工作缺乏有效的管理,致使分剂量药品的质量参差不齐,存在临床用药安全隐患。本文从儿科药品分剂量的需求、风险、政策法规和职业暴露等方面总结分析了国内儿科药品分剂量工作的现状及存在问题。同时结合经验提出了思考和建议,包括鼓励开发儿童适宜药品、评估风险、完善制度保障、探索新设备新技术、优化院内药品目录、加强宣传等,为我国儿科分剂量工作施行同质化管理和质量提升提供参考。     

基于全生命周期视角的国家药品标准管理思考

目的 为国家药品标准管理提供参考。方法 通过查阅文献,访谈药品标准领域专家,结合药品标准管理工作实践,运用生命周期理论对国家药品标准生命周期进行阶段划分,总结各阶段特点,并提出相应的管理建议。结果 国家药品标准生命周期可以划分为标准规划、标准制定和修订、标准贯彻实施和信息反馈4个阶段。针对标准规划科学、前瞻和可操作的特点,提出应当紧密结合我国医药行业发展现状、临床用药以及药品监管需要,全面收集药品标准需求,制定可操作且具有前瞻性药品标准规划的建议。针对标准制定和修订周期长,参与标准研究单位多,时间紧特点,提出应当遴选高水平研究单位参与标准制定和修订工作,并做好课题督导和绩效考核的建议。针对标准贯彻实施和信息反馈实践性强、信息量大、反馈意见急等特点,提出应当通过制定制度,将合理的反馈意见及时转化为标准或者标准研究课题的建议。结论 基于生命周期理论识别的国家药品标准各阶段特点可以为国家药品标准实践管理提供理论借鉴,有利于更全面、更系统地制定相应阶段应采取的策略。     

试论国家药品标准物质的稳定性及期间核查

目的 为做好国家药品标准物质期间核查工作提供参考.方法 介绍了国家对标准物质期间核查的基本要求及国家药品标准物质的稳定性核查工作,详细论述了稳定性的定义、影响药品标准物质稳定性的因素、保证药品标准物质稳定性的措施以及药品标准物质稳定性核查工作的原则、核查品种、核查间隔、核查项目、核查方法及核查结果评价等内容.结果与结论 国家药品标准物质是药品质量分析中使用的实物对照,也是药品检验不可缺少的物质.中国食品药品检定研究院将进一步加强药品标准物质的稳定性核查工作,以确保药品标准物质的有效性.     

全自动药品单剂量分包机在我院药房的应用情况与差错分析

目的：为进一步在医院药房推广应用全自动药品单剂量分包机提供参考。方法采用回顾性方法,对2014年1月至2014年6月住院药房TOSHOXana－4001CN全自动药品单剂量分包机的使用数据进行统计和分析。结果 TOSHOXana－4001CN全自动药品单剂量分包机操作简单,工作效率高,单剂量分包准确率达99．92％。结论全自动药品单剂量分包机改变了住院药房口服药调剂的传统工作模式,可有效提升药房工作质量和服务水平,降低药品差错率,保证临床用药的安全,值得推广。     

低剂量华法林对心房颤动患者脑卒中和凝血指标的影响

目的 探讨心房颤动患者低剂量长期使用华法林对患者脑卒中和凝血指标的影响。方法 选择2016年1月—2018年12月喀什地区第一人民医院收治的心房颤动患者213例作为研究对象,按照随机数字表法将患者分为3组,每组各71例。对照组患者使用阿司匹林肠溶片,200 mg/d。华法林高剂量组患者在使用华法林钠片前测定抗凝强度国际化标准比率（INR）作为基础值,初始剂量为2.5 mg/d,每隔3~5 d复查IRN,根据IRN调整使用剂量,每次增加0.625 mg,直至复查INR达标,达标时IRN值为2.1~3.0。华法林低剂量组患者使用华法林初始量为1.25 mg/d,每隔3~5 d复查IRN,达标时IRN值为1.5~2.0。根据IRN调整使用剂量,如果INR<1.5,每次增加0.625 mg,直至复查INR达标;如果INR>2.1,将华法林剂量减少0.625 mg。INR不稳定时,连续达标2次后以该剂量作为维持剂量,每月复查1次,直至INR达标。3组均治疗随访18个月。观察并比较两组患者的脑卒中发生情况、凝血指标、华法林用量、达INR标准时间和不良反应发生情况。结果 随访后,华法林高剂量组脑卒中发生率为2.82%,华法林低剂量组为4.23%,均明显低于对照组的14.08%,组间差异具有统计学意义（P<0.05）。治疗后,3组活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）均明显延长（P<0.05）,华法林高剂量和低剂量APTT、PT显著优于对照组,组间差异具有统计学意义（P<0.05）。华法林低剂量组华法林使用量和INR达标准值时间均明显低于华法林高剂量组（P<0.05）。治疗期间,华法林高剂量组出血、腹部不适等不良反应发生率为9.86%,华法林低剂量组为5.63%,均明显低于对照组的29.58%（P<0.05）。结论 心房颤动患者长期使用低剂量华法林能够有效的达到预防脑卒中的效果,其疗效与标准抗凝强度相当,且明显优于阿司匹林,具有较高的临床应用价值,可推广使用。     

Three-Stage Sequential Statistical Dissolution Testing Rules

Abstract

The U.S. Pharmacopoeia (USP) general monograph provides a standard for dissolution compliance with the requirements as stated in the individual USP monograph for a tablet or capsule dosage form. The USP monograph sets performance limit on dissolution in terms of a specific percentage Q that the drug product is required to be dissolved at a specified time. Japan Pharmacopoeia provides acceptance rules different from USP. However the objective of the acceptance rules was not defined in terms of the inference of the whole lot by either USP, European Pharmacopoeia (EP) or Japan Pharmacopoeia (JP). The operating characteristics’ curves of these rules are all shown to be sensitive to the true mean dissolution and do not reject a lot which has a large percentage of tablets that dissolve with less than the specified limit Q. This is especially true when the mean dissolution is close to the specification value. We proposed that the goal of the dissolution test sampling plan is to accept a lot at least 90% of the tablets dissolved more than a pre-specified amount Q at the specific time. The group sequential procedure derived accordingly is shown to outperform both USP and JP in controlling the type I error rate under normality assumption.     

Lack of Preventive Health Behaviors in the Early Forties: The Role of Earlier Trajectories of Cigarette Smoking From Adolescence to Adulthood

Objective: To study the degree to which individuals in different trajectories of cigarette smoking from adolescence to the early forties are similar or different in terms of lack of preventive health behaviors (e.g., underuse of preventive health services, unhealthy eating habits) in early midlife. Methods: Participants came from a community-based random sample of residents in two upstate New York counties (N = 548). Data were collected from adolescence to early midlife (mean age = 43 years, standard deviation [SD] = 2.8) at seven time points. Using growth mixture modeling, we statistically identified the number of smoking trajectories. Logistic regression analysis was used to study the relationship between the probabilities of participants' smoking trajectory group membership and lack of preventive behaviors in early midlife. Results: Five trajectory groups of cigarette smokers were identified. With controls, as compared with the nonsmoker trajectory group, higher probabilities of belonging to the heavy/continuous smoker trajectory group and the late starter trajectory groups were significantly associated with a higher likelihood of lack of preventive health behaviors (adjusted odds ratio [AOR] = 3.49 and 4.02 respectively). In addition, as compared to the quitter/decreaser trajectory group, higher probabilities of belonging to the heavy/continuous smoker trajectory group and the late starter trajectory group were also significantly associated with a higher likelihood of lack of preventive health behaviors (AOR = 3.51 and 4.04 respectively). Conclusions: Intervention programs may consider focusing on heavy/continuous smokers and late starters in programs designed to promote adequate use of preventive health services and healthy general lifestyles in early midlife.     

Analysis and Design of Clinical Trials Using Additive Hazards Survival Endpoints

Abstract–The additive hazards model provides benefits in interpretation and theoretical properties over the proportional hazards model, particularly in noninferiority trials. We describe techniques for designing and analyzing trials with a score-type test using the additive hazards model, with a focus on noninferiority trials. Accordingly, the techniques are illustrated using two noninferiority trials, the SPORTIF III trial of anti-coagulants for patients with atrial fibrillation, and the CPORT-E trial evaluating percutaneous coronary intervention in different clinical setting. We also derive a powerful test, which can be conducted using standard statistical software to distinguish between the additive and proportional hazards models. This test is shown to be effective in simulated data and applied to data from a study of melanoma as well as a study of colon cancer.     

Mammographic breast density by area of residence: possible evidence of higher density in urban areas

ABSTRACT

Objectives: A comparison of mammographic breast densities of women living in London with those of women living in rural and suburban areas.

Design and methods: Using the standard four American College of Radiology Breast Imaging Reporting and Data System (BIRADS) categories of mammographic density, 318 mammograms of women from London and 654 mammograms of women from outside the capital aged 27–87 years who had received mammography at the Princess Grace Hospital, London, were assessed for density. The association between having any dense tissue and area of residence was assessed using both ordered and standard logistic regression, giving odds ratio estimates of relative risk of dense tissue adjusting for age.

Results: Adjusting for age, London residents had significantly higher levels of density (OR = 1.32, 95% CI 1.04–1.70, p = 0.02). The major difference occurred in the age group 45–54 years and was most strongly manifested as a higher rate in London for density of 25% or more (BIRADS categories 2–4) as compared to almost entirely fatty (BIRADS 1) (OR = 2.22, 95% CI 1.05–4.68, p = 0.035).

Conclusion: The higher density is likely to be due to a different prevalence of risk factors in the London population. This study cannot ascertain the reason for the higher density in this urban population, but the result is a cause for concern given that screening uptake is lower in London. Increased attention to screening in urban areas and attention to screening quality for dense breast tissue might be prudent.     

Randomised clinical trial: a comparative study of 10-day sequential therapy with 7-day standard triple therapy for Helicobacter pylori infection in naïve patients

Aliment Pharmacol Ther 2012; 35: 56–65

Summary

Background The eradication rates following standard triple therapy for Helicobacter pylori infection are declining worldwide. Recent studies have shown that sequential therapy for H. pylori infection yields high cure rates. Aim To compare the efficacy and tolerability of a sequential regimen as first‐line treatment of H. pylori infection with a standard triple regimen. Methods A total of 348 naïve H. pylori‐infected patients from six hospitals in Korea were assigned randomly to standard triple or sequential therapy groups. Standard triple therapy consisted of 20 mg of rabeprazole, 1 g of amoxicillin and 500 mg of clarithromycin, twice daily for 7 days. Sequential therapy consisted of a 5‐day dual therapy (20 mg of rabeprazole and 1 g of amoxicillin, twice daily) followed by a 5‐day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily). Results The intention‐to‐treat (ITT) and per‐protocol (PP) eradication rates were 62.2% (95% CI 54.8–69.6%) and 76.0% (95% CI 68.5–83.5%) in the standard triple group, and 77.8% (95% CI 71.4–84.2%) and 87.9% (95% CI 82.3–93.5%) in the sequential group, respectively. The eradication rate was significantly higher in the sequential group compared with the standard triple group in both the ITT and PP populations (P = 0.002 and P = 0.013 respectively), whereas the incidence of adverse events was similar. Conclusions Ten‐day sequential therapy is more effective and equally tolerated for eradication of H. pylori infection compared with standard triple therapy. Sequential therapy may have a role as first‐line treatment for H. pylori infection.     

FDA对皮肤外用药活性成分人体最大用量试验的要求

美国食品药品管理局（FDA）于2018年5月发布了“考虑列入OTC专论的外用药活性成分的最大用量试验：研究要点和考虑的因素供企业用的指导原则”。最大用量试验（MUsT）是评估外用药体内生物利用度的标准方法,该指导原则对MUsT许多研究要点提出了具体的建议。详细介绍该指导原则的主要内容,期待对我国这方面的研究和监管有益。     

金莲花中药饮片质量研究

目的 研究金莲花中药饮片的质量考察方法。方法 采用表观检查、薄层色谱法、红外光谱法和高效液相色谱法系统考察金莲花饮片的质量。结果 对10批不同产地金莲花饮片的样品进行检查,其表观检查描述特征性较强,薄层色谱的斑点清晰、分离效果好,建立的金莲花饮片HPLC标准指纹图谱方法精密度、重复性、稳定性均良好,IR指纹图谱方法可进行快速分析。结论 采用多种方法对金莲花饮片进行了质量分析,并建立了一套比较完整的检查方法体系,对快速鉴别金莲花提供了一定的方法支撑,可用于金莲花饮片的质量分析与综合评价。     

Contrast Variable for Group Comparisons in Biopharmaceutical Research

Group comparisons can be conducted at three levels: (1) group means, (2) both group means and variabilities, and (3) group distributions. A traditional contrast is defined as a linear combination of group means; thus, traditional contrast analysis may only effectively address group comparisons in the first level. The concept of a contrast variable has recently been proposed. A contrast variable is defined as a linear combination of random variables (each variable representing random values in a group) instead of group means. Based on a contrast variable, we can use the mean of a contrast to address questions on group comparisons at the first level as in traditional contrast analysis. Meanwhile, we can use the ratio of mean to standard deviation of a contrast variable, that is, standardized mean of a contrast variable (SMCV), to effectively address questions at the second level. We can further use the probability that a contrast variable obtains a positive value, that is, c ⁺-probability, to effectively address questions at the third level. In this article, we explore the use of contrast variable, SMCV, and c ⁺-probability for comparing multiple groups in biopharmaceutical studies. Contrast variable, c ⁺-probability, and SMCV are applicable in a comparison context with or without independence and with or without homoscedasticity.