Prognostic factors in clinical trials

Summary Prognostic factors define the study population, help formulate the study objectives, and influence the treatment strategies. They must be accounted for in the study analysis to obtain valid estimates of the treatment differences and to evaluate results across studies. The causal relationship between a prognostic factor and the study endpoint can only be established through prospective randomized study designs. Potential factors discovered through retrospective analysis must be verified to establish their validity. Using such factors prematurely to select patient population and treatment strategy for a new study will not establish the validity of the potentially important factor.Supported by NCI 5 PO1 CA53996-15 and NCI 5 U10 CA38926-08.     

The spherical aberration of aphakic eyes corrected with intra-ocular lenses

The spherical aberration of eyes corrected with intra-ocular lenses is investigated using a model eye with realistic levels of corneal asphericity. The results indicate that the aberration is intermediate between that of paraxial schematic eyes and real eyes. By using standard optical aberration theory, it is shown that for a plano-convex lens with the curved surface facing the cornea, the aberration is similar to that of normal phakic eyes and therefore probably too low to be of any clinical significance. However, for other lens orientations or designs, the level of aberration is usually higher and may lead to a refractive error varying with pupil size and a loss of acuity with large pupil diameters.     

Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

MULTICENTER STUDY DESIGN OF THE EX VIVO EVALUATION OF ENDOCYTOSCOPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Optical technological innovations enable us to visualize cellular nuclei endoscopically. Herein is described a protocol design for a multicenter study for the ex vivo evaluation of endocytoscopy. The present study was performed by the Endoscopy Forum Japan study group.     

Practice of orthokeratology by a group of contact lens practitioners in Hong Kong

Purpose: The aim of the study was to provide information about the characteristics of three main types of orthokeratology (ortho‐k) lenses used in Hong Kong and to report on their performance based on the clinical impressions of a group of ortho‐k practitioners. Method: Twelve ortho‐k practitioners were interviewed between 1 March and 30 June 2001. Results: Most ortho‐k lenses were ordered from three manufacturers: DreimLens, Fargo and Contex. The median maximum myopia reduction reported for DreimLens, Contex and Fargo lenses were 6.25 D, 6.00 D and 4.50 D respectively. The time to reduce myopia by up to 4.00 D could be up to three weeks for Contex and DreimLens and up to four weeks for Fargo. For reduction of myopia by up to 4.00 D, the treatment usually required only one or two lenses per eye for all three types of lenses. The incidence of lens binding and lens tightening after achieving the optimal reduction was reported to be higher with the DreimLens design. Good centration, less lens binding, relatively lower incidence of complications and lens tightening after achieving the optimal reduction were reported with the Fargo lenses. Conclusions: DreimLens tended to be more effective for myopia reduction. However, some practitioners were concerned with the aggressiveness of myopia reduction using this lens design and the higher potential for ocular complications. Selection of the lens design is dependent on various factors, in particular, practitioners need to be comfortable with the design they choose and to consider the needs of their patients and the final goal of the treatment.     

经肝动脉灌注三氧化二砷对肝移植瘤血管的作用

目的 :探讨经肝动脉灌注As2 O3 对肝移植瘤血管的作用 .方法 :采用新西兰大白兔建立 5 0只肝脏Vx 2移植瘤动物模型 ,随机平均分成 5组 .移植瘤术后 2wk ,经肝动脉插管灌注不同浓度As2 O3 ,并以顺铂和生理盐水作对照 ,连续 7d ,6wk末切取肝肿瘤组织 ,观察肿瘤组织微血管有无改变 ,检测移植瘤组织血管内皮生长因子 (VEGF)的表达 .结果 :实验组肿瘤组织毛细血管内皮细胞肿胀、细胞核碎裂、细胞坏死及微血栓形成 ,阴性对照组和阳性对照组无类似改变 .实验组VEGF表达低于对照组 ,差异有显著性 (P <0 .0 1 ) ,而实验组间VEGF表达无差异性 (P =1 .0 0 ) .结论 :经肝动脉灌注As2 O3可减少肿瘤组织的血管生成 ;选择性破坏肝移植瘤组织血管 ,并存在一定剂量效应相关性     

医学微生物学"项目-导师制"实验教学改革初探

目的:探讨"项目-导师制"实验教学改革效果及其在医学微生物学实验教学中应用价值.方法:采用"项目-导师制"法对2001级学生进行医学微生物学实验教学,以无记名问卷调查和专家评议方式了解实验教学效果,以现场操作了解学生实验技能,以相对标准化试卷综合测试学生成绩,并与2000级学生医学微生物学实验教学效果、实验技能、考试成绩进行回顾性和对比分析.结果:2001级和2000级学生实验教学效果不满意、满意、很满意率分别为0%(0/180)、25.00%(45/180)、75.00%(135/180)和55.38%(72/130)、34.62%(45/130)、10.00%(13/130),差异有显著性(P＜0.01).实验技能考核及格、良好、优秀率分别为0%(0/180)、22.22%(40/180)、77.78%(140/180)和56.92%(74/130)、35.38%(46/130)、7.69%(10/130),差异有显著性(P＜0.01).综合考试成绩不及格、及格、良好、优秀率分别为0%(0/180)、17.78%(32/180)、47.22%(85/180)、35.00%(63/180)和154%(2/130)、38.46%(50/130)、52.31%(68/130)、7.69%(10/130),差异有显著性(P＜0.01).结论:"项目-导师制"实验教学是一种新型实验教学模式,可显著增强实验教学效果,帮助学生快速掌握实验技能,提高学生综合考试成绩,克服传统实验教学存在的一些弊端,具有应用推广价值.     

MR流量测定的实验研究

目的探讨MR流量测量与不同感兴趣区(ROI)直径的关系。方法使用Philips 1.5T双梯磁共振机流量测定程序,测量2mm内径塑胶管中不同流量的水(0.5、1.0、1.5、2.0、2.5ml/s),不同流向(流入及流出方向)、不同ROI位置(测量图中心区和偏中心区)与不同的ROI直径(直径0.5、1.0、1.5、2.0mm)流量变化关系,统计计算标准的ROI直径。结果在不同流量、流向和测量位置中,流量与ROI直径大小存在明显的直线相关(r>0.95,P<0.05),ROI直径大小显著地影响测量结果,当ROI直径取值等于测量图直径的0.6040±0.0480时,所测结果与实际流量一致。在不同流量下的不同流向及ROI位置对流量测定无影响(P>0.05)。结论对直径2mm流量测定,应选取测量图上直径的0.6040±0.0480 ROI进行。     

化疗药物性静脉炎及渗漏损伤的动物实验模型研究概况

化疗药物性静脉炎及渗漏损伤的动物实验模型是研究体内化疗药物性静脉炎及渗漏损伤的发病机制和评价各种治疗方法的重要条件。化疗药物性静脉炎及渗漏损伤的实验研究进展缓慢,其主要原因是缺乏理想的动物模型。依文献报道,化疗药物性静脉炎模型主要以大白兔耳缘静脉注射长春瑞滨等化疗药物为多见,化疗药物渗漏损伤模型主要以大鼠及大白兔背部皮下注射盐酸阿霉素等化疗药物为多见。文章就近年来常用的一些化疗药物性静脉炎及渗漏损伤的动物模型综述如下。