Virtual clinical trials are clinical trials conducted through computer simulation technology, which breaks through the limitations of traditional clinical trials and has the advantages of saving time, reducing costs, and reducing the risk of human trials. With the application of new computer technologies such as population pharmacokinetics, physiologically-based pharmacokinetics, quantitative systems pharmacology, and artificial intelligence, the field of virtual clinical trials in healthcare has become an important development direction. This article will give a preliminary review of the connotation, methods and future development trends of virtual clinical trials, aiming to provide reference for the application of new technologies and methods in clinical trials.
Population pharmacokinetics is a research technique based on computer simulation and data analysis, and it has been employed to investigate the dynamic behavior of drug metabolism in different populations. This approach could address practical challenges such as prolonged clinical trial durations, high costs, and increased difficulty in traditional clinical trials. By comprehensively analyzing differences in the internal drug metabolism processes across populations with varying physiological and pathological conditions, population pharmacokinetics has emerged as an effective method to optimize drug development and clinical applications. This article provides a preliminary overview of the essence of population pharmacokinetics, its application in clinical trials, and potential future trends. We hope to serve as a reference and guidance for the application of new technologies and methods in clinical trials.
Objective To systematically evaluate and comparatively analyze the mental health status of adolescents with different genders in middle schools of China, and to provide scientific evidence for the improvement of adolescents’ mental health level. Methods Such databases as CNKI, VIP, WanFang Data, and CBM (1989 to Dec, 2009) were searched. Data were extracted from the included literature and RevMan 4.2 software was used for meta-analyses. Results Twenty-seven original literatures were included. The results of meta-analyses showed: the total anxious trend of girls was higher than that of boys (OR= –?2.14, 95%CI –?2.93 to –?1.35, Plt;0.000 01); the result of each scale displayed that girls scored higher than boys in terms of study-anxiety (OR= –?0.53, 95%CI –?0.67 to –?0. 39, Plt;0.00001), social-anxiety (OR= –?0.30, 95%CI –?0.45 to –?0.15, Plt;0.000 1), self-accusation trend (OR= –?0.30, 95%CI –?0.46 to –?0.13, Plt;0.000 6), allergy trend (OR= –?0.18, 95%CI 0.31 to –?0.05, P=0.008), body symptom (OR= –0.21, 95%CI –0.34 to –0.08, P=0.001), and phobia trend (OR= –?0.80, 95%CI –?0.91 to –?0.68, Plt;0.000 01); No significant differences were identified between boys and girls in terms of solitude trend (OR=0.09, 95%CI –?0.04 to 0.22, P=0.2) and actuation trend (OR=0.06, 95%CI –?0.15 to 0.28, P=0.56). Conclusion Targeted measures should be taken for adolescent mental health education, especially for girls.
Objective To evaluate the clinical efficacy and safety of sparfioxacin in treatment of the acute respiratory tract infections. Methods A randomized-controlled clinical trial was carried out. Sparfloxaein 200 mg once daily and ofioxacin, as a control drug, 200 mg twice a day, both drugs were given by infusion for 7-14 days. There were 30 cases in each group. Results The clinical cure rates and the clinical efficacy rates of the two groups were 33.33%, 26.67%, and 80.00%, 76.67 % respectively. The bacterial clearance rates were 89.66% and 89.29% respectively. The adverse drug reaction rates were 13.33% and 16.67% respectively. There were no statistical differences between the two groups (Pgt;0.05). Photosensitive reaction was not observed in this study. Conclusion Sparfloxacin was effective in the treatment of the respiratory infections.
Objective To evaluate the clinical efficacy and safety of pazufloxacin for the treatment of moderate and severe acute bacterial respiratory infections.Methods A multicenter randomized controlled trial was conducted to compare the efficacy and safety of pazufloxacin versus levofloxacin. Patients in the pazufloxacin group were treated with pazufloxacin (500 mg twice daily for 7 to 10 days), and patients in the levofloxacin group were treated with levofloxacin (300 mg twice daily for 7 to 10 days). Results A total of 134 patients were enrolled in the study, 68 cases in pazufloxacin group and 66 cases in levofloxacin group were assessable for clinical efficacy by full analysis set(FAS). At the end of the treatment, in FAS analysis the total cure rates and effective rates were 52.9% and 86.7% in pazufloxacin group, 57.6% and 87.9% in levofloxacin group, in PPS analysis the total cure rats and effective rates were 57.1% and 93.7% in pazufloxacin group respectively, 61.3% and 93.6% in levofloxacin group. The bacterial clearance rates were 92.5% and 94.3% respectively. There were no statistically significant differences between the two groups. Adverse reactions were observed in 16.2% of patients in the pazufloxacin group and in 16.7% of patients in the levofloxacin group. These reactions were mainly local stimulation, nausea and diarrhea. No serious adverse event was reported in either group. Conclusion Pazufloxacin is as effective and safe as levofloxacin for the treatment of moderate to severe acute respiratory infections.
Objective To evaluate the safety and tolerance of pegfilgrastin (PEG-G-CSF) in Chinese healthy volunteers. Methods Thirty healthy volunteers were randomly divided into five single-dose groups to receive PEG-G-CSF 15, 30, 50, 60 or 75μg/kg by hypodermic injection. The safety profile and tolerability were evaluated by observing symptoms, vital signs, laboratory tests and electro cardiogram. Results No serious adverse event was reported for any volunteer. Transient dizziness occurred in one person in the 50 μg/kg dose group, and mild dizziness and ostalgia was found in all six people in the 75μg/kg dose group, of whom one experienced transient fever and two experienced mild diarrhea. No clinically significant changes in laboratory tests and electrocardiogram were found during the follow-up period. Conclusions The maximum tolerated dose of PEG-G-CSF injection in Chinese healthy volunteers is 60 μg/kg. Doses below 60μg/kg can be well tolerated. The recommended dose for phase II clinical trials is 60 μg/kgone, one dose for each cycle of chemotherapy.
目的 评价LB-SDS2.0型酸性氧化电位水生成机生成的酸性氧化电位水对皮肤（手）消毒的有效性和安全性。 方法 2006年2月－8月将90例健康志愿受试者随机分为3组，各组30例。A组用LB-SDS2.0型酸性氧化电位水生成机生成的酸性氧化电位水（试验产品）消毒2 min，B组用试验产品消毒4 min，C组（对照组）用聚维酮碘溶液擦拭3 min。检测消毒后菌落总数和致病菌，以及受试者不良反应情况。 结果 按照Ⅲ类区域工作人员洗手消毒标准，A、C组合格率均为100%，B组为96.7%；按照Ⅰ、Ⅱ类区域工作人员洗手消毒标准，A组合格率为86.7%；B组合格率为93.3%，C组合格率为100%。各组受试者试验后生命体征均无临床意义的改变，未出现任何不良反应。 结论 试验产品消毒手是安全有效的，可推荐用在Ⅲ类区域工作人员中使用，并进一步观察其安全性和有效性。建议扩大样本含量进一步评价其试验产品是否适用于Ⅰ、Ⅱ类区域工作人员洗手消毒。
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
目的 采用高效液相色谱法测定受试者口服埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片后血药浓度，评价埃索美拉唑肠溶胶囊的生物等效性。 方法 2009年9月－10月，36例健康男性受试者单次交叉口服埃索美拉唑肠溶胶囊（试验制剂）和埃索美拉唑镁肠溶片（参比制剂），测定给药后不同时间点血浆中埃索美拉唑经时血药浓度，采用DAS 2.0软件进行药物代谢动力学参数计算和生物等效性评价。 结果 受试者单次口服试验制剂与参比制剂后，达峰时间分别为（2.19 ± 0.96）、（2.43 ± 0.92） h，峰浓度分别为（1 748.86 ± 615.81）、（1 442.92 ± 476.41） μg/L，药时曲线下面积（AUC）0-t分别为（3 927.14 ± 1 839.10）、（3 878.79 ± 1 734.84） μg/L·h，AUC0-∞分别为（3 998.36 ± 1 866.22）、（3 918.31 ± 1 773.44） μg/L·h。试验制剂与参比制剂的生物等效性为94.0%，其90%CI为（82.3%，107.2%）。 结论 埃索美拉唑肠溶胶囊与埃索美拉唑镁肠溶片生物等效。
【摘要】 目的 评价麻敏维C缓释胶囊（每粒含盐酸伪麻黄碱90 mg和马来酸氯苯那敏4 mg）在人体的生物等效性。 方法 于2006年6月采用随机交叉自身前后对照试验设计，26例受试者分别单次和多次空腹口服麻敏维C缓释胶囊（试验制剂）和复方盐酸伪麻黄碱缓释胶囊（参比制剂），与不同时间点取血样，采用液-质联用（HPLC/MS）法测定人血浆中盐酸伪麻黄碱和马来酸氯苯那敏的浓度，以DAS软件计算药物代谢动力学参数，并进行生物等效性评价。 结果 单次给药后，两组分的主要药物代谢动力学参数无统计学意义（Pgt;0.05）。试验制剂中马来酸氯苯那敏和盐酸伪麻黄碱生物利用度分别为104.31%和109.19%。多次给药后，两组分的主要药物代谢动力学参数无统计学意义（Pgt;0.05）。试验制剂的马来酸氯苯那敏和盐酸伪麻黄碱的生物利用度分别为103.58%和99.37%。 结论 麻敏维C缓释胶囊和复方盐酸伪麻黄碱缓释胶囊具有生物等效性。【Abstract】 Objective To investigate the bioequivalence of delayed-release capsule of ephedrine-chlorphenamine-vitamin C. Methods In June 2006, 26 healthy volunteers were administrated with delayed-release capsule of ephedrine-chlorphenamine-vitamin C or delayed-release capsule of ephedrine-chlorphenamine in a randomized and two-way crossover design with single or multiple dosage. The plasma concentrations were determined by HPLC/MS method. The pharmacokinetic parameters and bioequivalence were calculated by DAS software. Results After single dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 104.31% in chlorphenamine and 109.19% in ephedrine, respectively. After multiple dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 103.58% in chlorphenamine and 99.37% in ephedrine, respectively. Conclusion Delayed-release capsule of ephedrine-chlophenamine-vitamin C is equivalent to the reference preparation.