Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view

Post-authorisation safety studies (PASS) of vaccines assess or quantify the risk of adverse events following immunisation that were not identified or could not be estimated pre-licensure. The aim of this perspective paper is to describe the authors’ experience in the design and conduct of twelve PASS that contributed to the evaluation of the benefit-risk of vaccines in real-world settings. We describe challenges and learnings from selected PASS of rotavirus, malaria, influenza, human papillomavirus and measles-mumps-rubella-varicella vaccines that assessed or identified potential or theoretical risks, which may lead to changes to risk management plans and/or to label updates. Study settings include the use of large healthcare databases and de novo data collection. PASS methodology is influenced by the background incidence of the outcome of interest, vaccine uptake, availability and quality of data sources, identification of the at-risk population and of suitable comparators, availability of validated case definitions, and the frequent need for case ascertainment in large databases. Challenges include the requirement for valid exposure and outcome data, identification of, and access to, adequate data sources, and mitigating limitations including bias and confounding. Assessing feasibility is becoming a key step to confirm that study objectives can be met in a timely manner. PASS provide critical information for regulators, public health agencies, vaccine manufacturers and ultimately, individuals. Collaborative approaches and synergistic efforts between vaccine manufacturers and key stakeholders, such as regulatory and public health agencies, are needed to facilitate access to data, and to drive optimal study design and implementation, with the aim of generating robust evidence.     

大学生网络成瘾与心身症状、社会支持及应付方式关系的研究

目的探讨大学生网络成瘾与心身症状、社会支持及应付方式的关系。方法采用多级分层整群抽样方法,采用《网络使用状况调查表》和《网络成瘾诊断量表》、《SCL-90症状自评量表》、《领悟社会支持量表》、《应付方式问卷》等心理量表,对唐山市3所大学在校大学生进行调查。结果唐山市大学生网络成瘾率为6.89%,男生网络成瘾率(8.71%)明显高于女生(5.99%)。网络成瘾者SCL-90测试躯体化、强迫症状、人际关系敏感、抑郁、焦虑、敌对、恐怖、偏执及精神病性各因子得分均高于非成瘾者。网络成瘾者领悟社会支持量表得分(61.20±10.90)低于非网络成瘾者(62.95±11.10)。网络成瘾者应付方式问卷自责、幻想、退避、合理化得分均高于非网络成瘾者,解决问题得分低于非网络成瘾者。结论大学生的网络成瘾率较高,且对大学生的心身健康产生明显影响,故应针对网络成瘾采取有效的预防和控制措施。     

儿童心脏外科手术用药和PASS应用的调查报告

目的:调查某儿童医院行心内直视手术病儿的用药及PASS对其审查的情况。方法:统计分析了2011年7～8月心胸外科的心内直视手术全部病例的用药情况及PASS对其审查的结果。结果:59例病儿用药品种累计80种,其中CICU和病房56种。术后24小时长期静脉用药8～13种。抗生素和抗真菌药物累计12种;单一使用42例;序贯6例,序贯及联合用药11例,分别选用2～8种,疗程10～30天。PASS黑色警示30次,发生率3.3%。结论:该组病儿同时用药品种多,时间长。必须加强临床合理用药的管理,PASS是有效手段之一。     

不同支抗控制可影响拔牙矫治中上颌第3磨牙的位置

中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B

Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.     

Patient acceptable symptom state and minimal clinically important difference for patient-reported outcomes in systemic sclerosis: A secondary analysis of a randomized controlled trial comparing personalized physical therapy to usual care

Background

To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc).

利用PASS2000估计临床试验期中分析效能及样本大小

目的：介绍统计软件包PASS2000在临床试验期中分析中的应用。方法：结合不同分析模块中各功能键及选项的含义说明该软件的功能。结果：通过具体实例分析说明其应用，其计算结果与当前通用方法结果一致。结论：该软件使用简单，结果准确、可靠，值得进一步推广、应用。