临床试验进展：适应性设计及透明性

临床试验中的适应性设计是根据累积信息来修正试验的一种设计方法,旨在使临床试验和临床开发计划效率更高,并为患者提供更加有效的治疗。此外,因信息隐匿造成试验失败和患者死亡,从而导致公众对医药行业的信任度下降,故关于公开临床数据的观点已开始朝着提升透明度方向调整。介绍3类适应性设计方法的特点和应用,以及国外药政部门和制药企业对提高临床试验透明性的举措。     

Information‐based sample size re‐estimation in group sequential design for longitudinal trials

Group sequential design has become more popular in clinical trials because it allows for trials to stop early for futility or efficacy to save time and resources. However, this approach is less well‐known for longitudinal analysis. We have observed repeated cases of studies with longitudinal data where there is an interest in early stopping for a lack of treatment effect or in adapting sample size to correct for inappropriate variance assumptions. We propose an information‐based group sequential design as a method to deal with both of these issues. Updating the sample size at each interim analysis makes it possible to maintain the target power while controlling the type I error rate. We will illustrate our strategy with examples and simulations and compare the results with those obtained using fixed design and group sequential design without sample size re‐estimation. Copyright © 2014 John Wiley & Sons, Ltd.     

Biomarker driven population enrichment for adaptive oncology trials with time to event endpoints

The development of molecularly targeted therapies for certain types of cancers has led to the consideration of population enrichment designs that explicitly factor in the possibility that the experimental compound might differentially benefit different biomarker subgroups. In such designs, enrollment would initially be open to a broad patient population with the option to restrict future enrollment, following an interim analysis, to only those biomarker subgroups that appeared to be benefiting from the experimental therapy. While this strategy could greatly improve the chances of success for the trial, it poses several statistical and logistical design challenges. Because late‐stage oncology trials are typically event driven, one faces a complex trade‐off between power, sample size, number of events, and study duration. This trade‐off is further compounded by the importance of maintaining statistical independence of the data before and after the interim analysis and of optimizing the timing of the interim analysis. This paper presents statistical methodology that ensures strong control of type 1 error for such population enrichment designs, based on generalizations of the conditional error rate approach. The special difficulties encountered with time‐to‐event endpoints are addressed by our methods. The crucial role of simulation for guiding the choice of design parameters is emphasized. Although motivated by oncology, the methods are applicable as well to population enrichment designs in other therapeutic areas. Copyright © 2014 John Wiley & Sons, Ltd.     

自适应统计迭代重建技术算法在头颅CT扫描降低噪声中的对比分析

目的：分析不同的ASIR（自适应统计迭代重建技术）值在降低头部图像噪声中的价值。方法：采用型号为Discovery CT750 HD的宝石CT,对32例受检者进行头部扫描。扫描结束后在双侧侧脑室最大层面重建图像,FOV25cm、层厚5mm、间隔20mm,共5层,分别将ASIR值设定为0％、20％、40％、60％、80％、100％重建图像,窗宽为100HU、窗位为35HU。在一侧侧脑室内选取圆形感兴趣区,测量不同的ASIR值时侧脑室脑脊液的CT值与标准差,应用医学统计软件SPSS13对数据进行统计分析。结果：各组间侧脑室脑脊液的CT值标准差有明显的统计学差异,随ASIR百分比的增加,图像噪声水平明显降低。结论：提高ASIR值能够降低图像噪声。扫描时,采用较高ASIR值具有降低射线剂量的作用。     

径向基函数自适应减法器提取诱发电位的性能评价

目的：针对体感诱发电位（somatosensory evoked potentials,SEP）的特征,基于现场可编程门阵列（field programmable gate array,FPGA）硬件平台设计径向基函数自适应减法器,实现体感诱发电位的快速提取。方法：通过对各模块的硬件算法设计,利用Simulink仿真工具对5例接受脊柱侧弯手术患者的原始SEP信号进行仿真实验,以工频干扰、EEG脑电为噪声,对径向基函数自适应减法器提取SEP的性能进行评价。结果：不同输入信噪比条件下,径向基函数自适应减法器比单一自适应减法器输出信号的信噪比高;输入信噪比为-15dB时,单一的自适应噪声减法器（adaptive noise canceller．ANC）输出相对于模板信号的失真比径向基函数自适应减法器（ANC—RBF）小,但输入信噪比为-25、-30dB时,ANC输出相对于模板信号的失真比ANC—RBF大;ANC—RBF提取的SEP波形比较平滑。结论：径向基函数自适应减法器比单一自适应减法器对术中体感诱发电位具有更好的去噪效果,不仅提取信号的失真度较小,而且信号波形更为平滑,使SEP信号的潜伏期和幅值更易识别。     

Tourette综合征儿童主观生活质量和社会适应能力的研究

目的 分析 Tourette 综合征(Tourette syndrome,TS)儿童的主观生活质量和社会适应能力,为临床治疗提供指导依据。方法 采用儿少主观生活质量问卷(Inventory of Subjective Life Quality,ISLQ)、儿童行为量表(Children Behavior Checklist,CBCL)、儿童适应行为评定量表(Social of Adaptive Behavior,SAB),对112例 TS 儿童( ≥8岁)的主观生活质量和社会适应能力进行对照研究。结果 TS 患儿 ISLQ 中有7个维度得分明显低于对照组(P＜0.01);行为问题得分明显高于对照组(P＜0.05)。适应能力商数(adaptability quotient,ADQ)低于对照组(P＜0.05),其中认知功能、社会/自制两项与对照组差异有高度统计学意义(P＜0.001)。结论 TS 儿童的主观生活质量和社会适应能力存在诸多问题,及时进行合理干预,有助于促进 TS儿童身心康复。     

图像滤波技术在B型超声诊断仪中的应用研究

目的：依据医学超声图像固有特点,对B型超声医学图像滤波技术进行研究,以达到大幅度提高图像质量的目的。方法：通过Matlab等工具实现B型超声诊断仪图像的均值滤波、中值滤波、自适应中值滤波、小波变换以及各向异性扩散方程滤波。结果：对常见的B型超声诊断仪滤波算法进行了比较与研究。结论：所有的滤波方法对图像信号均有一定程度的增强,对噪声亦有抑制。均方误差反映了滤波图像在抑制噪声的同时,对细节的保持情况和超声医学图像两者之间达到一个最佳的平衡。     

An update on leptin as immunomodulator

Until the discovery of leptin 20 years ago, adipose tissue was considered only as a fat storage organ, involved in the regulation of energy homeostasis. At present, it is well known that adipokines, being leptin the forerunner of this superfamily, may act in different biological processes, including inflammation and immunity. In this review, we have explored the recent evidence about the relationship between leptin and immune system, summarizing the most important findings related to the involvement of leptin in both innate and adaptive immune response.