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.     

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.     

提高中医临床疗效的科学学检讨(连载三)

中医学的生命力在于临床疗效 ,社会对于中医学的需要也在于临床疗效。提高中医临床疗效的科学学研究 ,要以中医基础理论为依据 ,以理、法、方、药一脉相承的辨证论治为前提。造成中医临床疗效下降的问题在于“三个脱节” ,即中医学与自身文化基础脱节 ,中医临床与辨证论治脱节 ,中药与中医临床脱节。中医学正处于行将消亡的边缘 ,也处在新的突破的前夜。实事求是地进行科学、历史的反思 ,中医学完全有可能走出百年困惑 ,得到振兴和发展。     

高危人群微量乙肝疫苗免疫效果动态观察

采用微量乙肝疫苗（总剂量为６μｇ）对ＨＢＶ高流行区居民进行随机对照研究，免疫Ⅰ组（疫苗＜８℃保存）Ｔ１２抗体阳转率和保护率分别为９０．８％和８７．０％，和对照组相比，差异显著（Ｐ均＜０．００１）；和常规剂量（总剂量９０μｇ）比，其抗体阳转率和保护率基本相同。提示ＨＢＶ高流行区可用微量乙肝苗代替常量乙肝苗进行预防接种。免疫Ⅰ组和免疫Ⅱ组（乙肝疫苗室温保藏２８℃±）免疫效果和保护率基本相同，认为室温条件下乙肝疫苗６个月内效价不变。     

A Comparative Study of Dihydroartemisin in Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

Objective: To compare the safety and efficacy of two compounds of dihydroartemisinin(DHA) -Artekin and Artekin (T) in the treatment of uncomplicated falciparum malaria. Methods:The regimen of 8-tablet for 2 days of Artekin and Artekin (T) were applied to 100 patients with uncomplicated falciparum malaria, who were randomly divided into two groups. Each group contained 50 cases. The cure rate, the mean parasites clearance time, the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compounds used. Results: The mean parasites clearance time was 31. 7±9.0 hours in the Artekin group and 32. 8±8. 8 hours in Artekin (T) group respectively; the mean fever clearance time was 12. 7±7. 2 hours in Artekin group and 16. 5±7. 9 hours in Artekin (T) group; there were no recrudescence case in both groups within the 28 days of follow-up, the cure rates in Artekin group and Artekin (T) groups were 100%. It indicated that the tolerability of both compounds were very good, the     

后房型人工晶体植入术后早期并发症临床分析及处理

报告468例500眼后房型人工晶体植入术后2周内出现的并发症发生率,其中角膜水肿73.6％,色素膜炎症反应88.4％,瞳孔变形12.8％,人工晶体表面渗出膜3.8％,后囊混浊13.8％,短暂性高眼压5.2％,晶体皮质残留5.8％,人工晶体偏位2.6％,前房出血3％。提高术后视力的关键是提高手术技巧以减少并发症的发生。     

美宝湿润烧伤膏治疗急性肛裂疗效观察

目的：对美宝湿润烧伤膏(MEBO)、肛裂膏外用治疗急性肛裂进行疗效分析，判断其优劣。方法：将2000-2002年我院治疗的188例急性肛裂患者随机分为A组和B组，两组均采用相同的全身治疗，其中A组采用MEBO外用，B组采用肛裂膏外用。通过跟踪随访，在平均愈合时间、治愈率两方面进行判断分析，比较优劣。结果：A组在平均愈合时间、治愈率方面均优于B组。结论：湿润烧伤膏外用治疗急性肛裂优于肛裂膏，为治疗急性肛裂较好的外用药。     

优立新治疗急性细菌性感染的临床观察

优立新与头孢噻肟随机对照治疗呼吸道和泌尿道感染４０例，临床有效率各为１００％和９５％（Ｐ＞０．０５），细菌阴转率各为９４，１％和１００％（Ｐ＞０．０５）。无显著性差异。优立新共治疗３０例，临床有效率和细菌阴转率分别为１００％和９６％。两药副反应均轻微。无因副反应而停药。在优立新治疗病例中，有２例出现皮疹。另２例为肝功能ＡＬＴ和ＡＳＴ暂时性轻度增高。