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.
Since the outbreak of the coronavirus disease (COVID-19), more than 200 interventional clinical trials have been registered in Chinese Clinical Trial Registry (www.chictr.org.cn) and the US Clinical Trials Registry (www.clinicaltrials.gov), testing or going to test treatments of COVID-19 in China from January 23rd, 2020 to March 5th, 2020. This situation has drawn attentions from various sectors of society. This article summarizes the basic design features of 249 registered COVID-19 clinical trials in China, compares them with National Clinical Trials Network practices in the USA, and describes a concept of national clinical trials network as a strategy to enhance quality and efficiency of clinical research in cases like COVID-19 outbreak as well as other disease fields.
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.
Early and mid-stage esophageal cancer can achieve a particular effect through surgeries or comprehensive treatment based on surgery. Once the esophageal cancer progresses to the advanced stage, it is still lack of effective remedy for the disease, and the patient's prognosis is poor. Immunotherapy has developed rapidly in recent years, bringing dawn to patients with advanced esophageal cancer. On July 31, 2019, the US Food and Drug Administration (FDA) approved KEYTRUDA (Merck) for the treatment of esophageal squamous cell carcinoma, and it became the first milestone drug for esophageal squamous cell carcinoma. In the paper, we will review the progress of immunotherapy in the treatment of advanced esophageal cancer on the basis of current clinical researches, which might provide ideas for further studies in the immunotherapy for esophageal cancer.
Artificial intelligence (AI) for science (AI4S) technology, the AI technology for scientific research, has shown tremendous potential and influence in the field of healthcare, redefining the research paradigm of medical science under the guidance of computational medicine. We reviewed the main technological trends of AI4S in reshaping healthcare paradigm: knowledge-driven AI, leveraging extensive literature mining and data integration, emerges an important tool for understanding disease mechanisms and facilitating novel drug development; data-driven AI, delving into clinical and human-related omics data, unveils individual variances and disease mechanisms, and further establishes patient-centric digital twins to guide drug development and personalized medicine. Meanwhile, based on authentic patient digital twin models, adaptable strategies are employed to further propel the development of "e-drugs" that mimic the authentic mechanisms. These digital twins of drugs are evaluated for drug efficacy and safety through large-scale cloud-based virtual clinical trials, and followed by rationally designed real-world clinical trials, thus notably reducing drug development costs and enhancing success rates. Despite encountering challenges such as data scale, quality control, model interpretability, the transition from science insights to engineering solutions, and regulatory hurdles, we anticipate the integration of AI4S technology to revolutionize drug development and clinical practices. This transformation brings revolutionary changes to the medical field, offering novel opportunities and challenges for the development of medical science, and more importantly, providing necessary but personalized healthcare solutions for humankind.
目的 为避免选择和发表偏倚,系统评价者应采用多种查询技术,并尽力获得未发表的研究.本文试图探讨,英特网检索对鉴定未发表和正在进行的临床试验是否有用.研究设计 利用七个Cochrane系统评价的查询策略回顾性地在英特网上检索未纳入的随机对照试验.方法 检索策略 以普通检索式"研究方法学 NEAR干预措施NERA 条件"、用AltaVista在英特网上搜索.测量指标包括搜索时间、英特网搜索已发表研究的回溯率、精确度(已发表和未发表的随机临床试验链接的网页比例)、英特网检索到的未纳入的未发表和正在进行的研究数.结果 用21小时查询了429个网页,找到14个链接到未发表的、正在进行的或最近完成的试验,至少有9个与4篇系统评价相关.英特网检索已发表研究文献的回溯率在0～43.6%,其链接已发表和未发表研究的精确度在0～20.2%.结论 未发表尤其是正在进行的试验的信息可在英特网上找到.潜在的问题是如何评价未经同行评审的电子出版物的质量.急需更强的搜索工具.建议用"Open Trial Initiative"定义英特网发表试验的语法,以加强试验登记的共同操作性.因此,专门的搜索引擎可找到更多有关正在进行和已完成的临床试验信息.
Clinical trial transparency, include clinical trial registration, unbiased reporting results and sharing individual participant data (IPD), is one of the most important revolutionary concepts following clinical epidemiology and evidence-based medicine in the medical field. Sharing IPD is a medical ethics issue reflected a new sense of worth and constructing new rules of clinical trials. Our viewpoint is that from the essential purpose of clinical research, IPD is a social public property. Sharing IPD is a one of the best ways for respecting the contributions of the participants, and one of the keys for changing face of clinical trials.
Objective To assess the safety and effect of different intravenous chemotherapic regimens in patients with gastric carcinomas who had received gastrectomy. Method A systematic review of all the relevant randomized controlled trials (RCTs) was performed. RCTs were identified from Medline and Embase (1980-2001.4), Chinese Bio-medicine Database (1990-2001.1). Literature references were checked at the same time. We included randomized andquasi-randomized trials in patients with confirmed gastric carcinomas who had received gastrectomy comparing the effect of intravenous chemotherapy after gastrectomy with that of gastrectomy alone.Results Twenty trials involving 4 171 patients were included. Meta-analysis was done with fixed effects model. Heterogeneity analyses was performed also. The effects of intravenous chemotherapy with 5FU + MCCNU, 5FU + MMC, 5FU + BCNU or FAM after gastrectomy were failed to show have better effects than that of surgery alone. There were eleven trials which detailed the side effects according to the toxicity grade by WHO standard. The side effects halting treatment were haematologic and biochemical toxicity, debilitating nausea and vomiting. There were twenty-two patients died of chemotherapic toxicity. Conclusions Based on the review, there is no enough evidence to show that intravenous chemotherapy after gastrectomy have positive treatment effect on gastric cancer.
Objective To identify and investigate the quality of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) in 11 non-key Chinese medical journals so as to learn about the current status and problems. Methods Eleven non-key medical journals of TCM from 1995 to 2000 were hand searched to identify the RCT and controlled clinical trials (CCTs). Each identified RCT or CCT was page by page verified by handsearchers based on the criteria developed by the Cochrane Handbook; the RCTs’ design, randomization method description, blind, baseline comparison, inclusion and exclusion criteria, diagnostic criteria,criteria for theraputic effectiveness, sample size, statistical method，described outcome, side effects, and follow up etc. were analyzed. Results In the related journals from 1995 to 2000, a total of 66 volumes and 390 issues were checked. As a result, 22 739 clinical studies were identified, of which 1 416 RCTs, only 24 (1.69%) were done with double blinding. There were 141 CCTs from 1995 to 2000, the total number of RCT increased from 95 to 1 416 and most of studies were on digestives diseases. Most of these studies had no detailed randomization method description, only 38 (2.68%) studies provided a methodology description. In addition, 1 220 (86.16% ) described outcome index, 1 203 (84.96%) used statistical method，934 (65.96%) had baseline comparison，828 (58.47%) described diagnostic criteria, 197 (13.91%) had inclusion and exclusion criteria，finally only 89 (6.29%) reported side effects. Conclusions Although the number of RCT has increased in the 11 non-key medical journals of TCM in the past six years, the quality of these RCTs needs to be improved.
Objective To assess the efficacy and safety of Chinese medicinal herbs for asymptomatic hepatitis B virus(HBV) infection. Data Source The trials registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the Cochrane Complementary Medicine Field were searched in combination with MEDLINE, EMBASE, and handsearches of Chinese journals and conference proceedings. Data Selection Randomized clinical trials with 3 months follow-up comparing Chinese medicinal herbs versus placebo, no intervention, non-specific treatment, or interferon treatment for asymptomatic HBV carriers were included. No language and blinding limitations were applied. Data Extraction Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad-scale plus allocation concealment. Results Three randomized clinical trials (307 patients) with low methodological quality following patients for three months or more after the end of treatment were included. Herbal compound Jianpi Wenshen recipe showed significant effects on clearance of HBV markers compared to interferon: relative risk 2.40 (95 % CI 1.01 to 5.72) for clearance of serum HBsAg, and 2.54 (1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomized clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. No serious adverse event was observed. Conclusions There is insufficient evidence for treatment of asymptomatic HBVcarriers using Chinese medicinal herbs due to the low quality of the trials. Further randomized, double blind, placebo-controlled trials are needed.