Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

《艾滋病诊疗指南第三版(2015版)》更新解读

2015年中华医学会感染病学分会艾滋病学组发布了第三版《艾滋病诊疗指南》。新版指南强调抗病毒治疗时点前移:一旦成人确诊感染人类免疫缺陷病毒(HIV), 若无禁忌宜尽早启动抗HIV治疗。对于合并机会性感染的HIV感染者, 在感染控制、病情稳定后也应及早开始抗病毒治疗。尤其强调HIV合并结核患者在CD4阳性淋巴细胞数少于200/μL的情况下, 建议抗结核两周内即开始抗病毒治疗。在抗HIV治疗用药中, 淘汰了一些毒副作用大、依从性较差的药物, 如司他夫定、去羟肌苷、茚地那韦等, 优选抗病毒效力强、服药方便的组合, 如拉米夫定、替诺福韦、依非韦伦组合。对于HIV感染的婴幼儿, 亦主张及早抗HIV治疗。对于五岁以内的幼儿, 主张确诊后即启动抗病毒治疗。对于HIV感染的孕产妇, 建议尽快予以全程、联合抗HIV治疗, 寓防于治。     

腹腔镜与开腹手术治疗老年胆囊炎患者的分析

目的观察在治疗老年急性胆囊炎患者采取开腹手术与腹腔镜手术的治疗效果并分析。方法将2017年1月—2018年9月期间医院收治的74例急性胆囊炎患者采用随机数字表法分为观察组和对照组,对照组37例采取开腹手术治疗,观察组37例采取腹腔镜治疗,对比两组治疗效果。结果观察组并发症发生率5.4%、治疗总有效率97.3%优于对照组的24.3%、78.4%,P<0.05。观察组术中出血量(15.7±3.4)mL、手术时间(40.7±4.4)min、住院时间(7.1±1.8)d、术后肠道恢复时间(3.3±1.2)d均低于对照组的(46.4±3.5)mL、(68.6±14.7)min、(12.6±2.3)d、(6.1±1.5)d,P<0.05。观察组躯体疼痛(87.3±0.5)分、总体健康(85.2±1.2)分、精神状况(86.4±1.3)分、社会活动评分(90.2±1.3)分均高于于对照组(78.3±1.2)分、(70.3±10.8)分、(71.3±0.5)分、(75.5±2.1)分,对比有统计学意义(P<0.05)。结论腹腔镜手术治疗老年急性胆囊炎患者效果良好,可有效减少患者病程,促进康复和提高生活质量,值得推广。     

微波配合序贯扩肛治疗陈旧性肛裂患者的临床分析

目的:探讨微波配合序贯扩肛治疗陈旧性肛裂的临床疗效。方法:选取陈旧性肛裂患者78例,随机分为对照组和治疗组,每组各39例。对照组患者采用后卫内括约肌部分切断治疗,治疗组患者采用微波配合序贯扩肛治疗。结果:观察组患者术中出血量、切口愈合时间均少于对照组(P<0.05),并发症发生率低于对照组(P<0.05)。结论:采用微波配合序贯扩肛治疗陈旧性肛裂,临床疗效显著。     

Pseudoaneurysm in the inferior alveolar artery following a bad split in bilateral sagittal split osteotomy

Pseudoaneurysms in the external carotid artery system are rare, mostly reported in the superficial temporal and facial arteries. The bilateral sagittal split osteotomy has a low incidence of complications requiring emergency interventions. We report the case of a patient with acute bleeding from a pseudoaneurysm of the inferior alveolar artery diagnosed by angiography and treated successfully by super-selective embolization.     

Effects of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer: A protocol of randomized controlled trial

Background:Gastrointestinal complications and malnutrition are common problems that affect postoperative rehabilitation and survival of patients with esophageal cancer. Evidence has shown that probiotics have a positive effect on improving gastrointestinal complications and nutritional status of patients with esophageal cancer after surgery, but there is a lack of prospective studies on this topic. We designed this prospective randomized controlled trial to evaluate the effects of probiotics on gastrointestinal complications and nutritional status in patients with postoperative esophageal cancer.Methods:This is a prospective, randomized, double-blind, placebo-controlled trial. It was approved by the Clinical Research Ethics Committee of our hospital. 192 patients will be randomly divided into probiotics group and the placebo group in a 1:1 ratio. After operation, probiotics and placebo will be given orally for 8 weeks. The indexes of nutritional status and incidence of digestive tract complications will be recorded and the data will be analyzed by SPSS 18.0 software.Discussion:This study will evaluate the effect of probiotics on gastrointestinal complications and nutritional status of postoperative patients with esophageal cancer. The results of this study will provide clinical basis for the use of probiotics in postoperative treatment of esophageal cancer.Trial registration:OSF Registration number: D DOI 10.17605/OSF.IO/QHW86     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.