外国制药企业在中国开展临床试验现况分析——基于Clinical Trials.gov网站登记数据的统计分析

目的:本文通过查阅ClinicalTrials.gov网站数据库登记的有关内容,对在中国开展的临床试验进行了归纳总结和分析。方法:"ClinicalTrials.gov"是全球最大的临床试验登记网站,提供由企业或政府申办的最新的有关临床试验的情报。通过查阅2007年5月8日前所登记注册临床试验的检索结果,对外国制药企业在中国进行的独立开展或参与国际多中心临床试验登记数据进行了统计分析。结果:在中国,由制药企业赞助的临床试验有97件,其中58件是国际多中心试验,39件是中国单独进行的试验。主要的研究对象疾病为肿瘤、循环系统疾病、中枢系统疾病及感染。在中国单独试验中,临床试验受试药均为在海外上市的药,这些试验的目的是为了在中国扩大适应症或是为了进口中国。而在国际多中心试验中的受试药有在海外处于IV期,还有处于III期,这些试验的目的是为了取得中国人的试验数据或是为了促销而进行的。在中国单独试验中有一半,在国际多中心试验中有67%是随机双盲试验。中国临床试验的特点是参加医院数集中在10个左右。结论:外国制药企业让中国参与更多的国际多中心临床试验,加快新药研发进程。

Time-to-enrollment in clinical trials investigating neurological recovery in chronic spinal cord injury:observations from a systematic review and Clinical Trials.gov database

Currently,large numbers of clinical trials are performed to investigate different forms of experimental therapy for patients suffering from chronic spinal cord injury(SCI).However,for the enrollment process,there are different views on how the time period between injury and interventions should be determined.Herein,we sought to evaluate the impact of time-to-enrollment in chronic SCI clinical trials.A data set comprising 957 clinical studies from clinical Trials.gov was downloaded and analyzed focusing on the eligibility criteria for post-injury time-to-enrollment.We also aggregated individual patient data from nine clinical trials of regenerative interventions for chronic SCI selected by a systematic literature search from 1990 to 2018.Characteristics of the studies were assessed and compared by dividing into three groups based on time-to-enrollment(group 1≤12 months,group 2=12-23 months and group 3≥24 months).In Clinical Trials.gov registry,445 trials were identified for chronic SCI where 87%(385)were unrestricted in the maximum post-injury time for trial eligibility.From systematic literature search,nine studies and 156 patients(group 1=30,group 2=55 and group 3=71)were included.The range of time-to-enrollment was 0.5 to 321 months in those studies.We also observed various degrees of motor and sensory improvement in between three time-to-enrollment groups.Our results indicate that enrolling wide ranges of time-to-enrollment in a group may present imprecise outcomes.Clinical trial designs should consider appropriate postinjury time frames to evaluate therapeutic benefit.

基于Clinical Trials数据库的癌性疼痛治疗药物临床试验分析

目的了解近年来癌性疼痛(癌痛)治疗药物临床试验的趋势和特点,为癌痛治疗药物的开发和临床研究提供参考依据。方法从Clinical Trials数据库中检索1987—2022年癌痛治疗药物临床试验的相关信息,从试验类型、备案时间、申报地区、癌痛类型、癌痛治疗药物等角度进行描述性分析。结果筛选出临床试验376项,由研究者发起的试验(IIT)项目数多于注册类试验(IST),其中北美洲的总项目数、IIT和IST项目数最多;试验总项目数和IST项目数先增长后回落,IIT的试验项目数稳步增长。针对慢性癌痛、爆发性癌痛和重度癌痛的研究相对较多。研究对象以阿片类药物尤其是芬太尼的占比最高。结论癌痛治疗药物临床试验对推进癌痛治疗药物治疗发挥了重要作用,未来有待进一步加强IST在新型癌痛治疗药物的研究和开展更多IIT研究,以更好地优化癌痛治疗效果。

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Current clinical trials on gastric cancer surgery in China

Gastric cancer(GC)is the leading diagnosed malignancy worldwide,especially in China.Radical surgery is the cornerstone of GC treatment.We reviewed previous clinical trials and aimed to provide an update on the factors related to the surgical treatment of GC.The number of registered clinical trials in the field of GC surgery is rapidly increasing.With the development and popularization of endoscopic,laparoscopic,and robotic techniques,GC surgery has gradually entered a new era of precise minimally invasive surgery.Postoperative quality of life has become a major issue in addition to surgical oncological safety.Although great progress has been made in clinical research on GC in China,there are still deficiencies.Many studies enrolled large numbers of patients,but the research data were not of high quality.The characteristics of GC in China include a high incidence,large population,and large proportion of patients with advanced GC,which provides sufficient reason for studying this disease.There is still a need for well-designed,large,randomized clinical trials to improve our knowledge of the surgical treatment of GC.

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment

AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.

Anti-oxidative stress treatment and current clinical trials

Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

基于ClinicalTrials.gov的全球数字疗法临床试验注册现状研究

目的研究全球数字疗法临床试验注册现状,为数字疗法的临床研究及应用提供参考。方法在ClinicalTrials.gov中检索数字疗法相关临床试验,运用文献计量学方法,分析全球数字疗法临床试验的注册数量和年度变化趋势、国家/地区分布及合作情况、申办者类型及构成情况、研究类型及试验分期、适应证分类和特征。结果全球数字疗法相关临床试验共2960项,其中美国最为活跃,远超其他国家/地区,与德国同处国际合作的中心,申办者中64.79%是高校/医院,美国高校/医院表现突出。85.44%是干预性研究,大多数属于设备和行为干预,适应证集中于精神疾病、慢性病和神经系统疾病领域,包括焦虑症(109项)、抑郁症(103项)和肥胖(101项)。截至检索日期,我国数字疗法相关临床试验为143项,与美国存在较大差距。结论全球数字疗法临床试验呈现逐年增长趋势,受COVID-19大流行影响,2020年后增长显著。我国数字疗法尚处于起步阶段,全面推广及应用尚需时间。

Knowledge and Attitudes of Oncology Nurses Toward Clinical Trials-A Secondary Publication

Purpose:The purpose of this study was to identify the knowledge and attitudes of oncology nurses toward clinical trials and to provide evidence for the development of clinical trial education programs for oncology nurses.Methods:The study was conducted on 142 nurses who had more than six months of nursing experience working with cancer patients at a tertiary hospital in Seoul,Korea.A structured questionnaire was used to measure the knowledge and attitudes of oncology nurses toward clinical trials.Results:The participants scored an average of 15.03±3.52 out of 19 in terms of knowledge about clinical trials.In terms of attitudes toward clinical trials,the participants scored an average of 5.91±1.37 out of 8.There was a significant positive correlation between the knowledge and attitudes of the participants toward clinical trials(r=0.23,P=0.007).Conclusion:This study found that there was a relationship between the knowledge and attitudes of oncology nurses toward clinical trials.To improve the competency of oncology nurses and provide high-quality care to patients participating in clinical trials,more systematic and sustainable education is required.

An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China

Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.

Comparative Study on the Policy of Multiplicity Issues in Clinical Trials at Home and Abroad

Objective To study the content of China’s guiding principles on multiplicity issues in clinical trials,and to provide reference for the revision of China’s relevant guiding principles.Methods Based on ICH E9,the similarities and differences of the guiding principles of US Food and Drug Administration(FDA),European Medicines Agency(EMA),and National Medical Products Administration(NMPA)on the multiplicity issues in clinical trials were compared one by one.Results and Conclusion In general,NMPA guidelines are based on ICH E9,but in detail,the guidelines of FDA and EMA focus differently on the multiplicity issues.Therefore,NMPA guidelines need to be detailed and comprehensive.NMPA guidelines can be refined by referring to foreign guidelines to improve the practical guiding significance for clinical research and promote the level of domestic clinical trials in line with international standards.

Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。

基于ClinicalTrials.gov探讨慢性胰腺炎治疗研究新进展

慢性胰腺炎(chronic pancreatitis,CP)是指各种病因引起的胰腺慢性进行性炎症性纤维化疾病,临床表现为反复发作的上腹部疼痛和胰腺外分泌功能不全.ClinicalTrials.gov是目前国际上应用最广泛的临床试验数据库,主要包含已完成的、正在开展的和即将进行的临床研究的信息.本文通过对ClinicalTrials.gov数据库中所有于2024-06-30前注册的临床研究进行检索,筛选出最新的CP相关的临床研究,从营养支持、药物、内镜等角度整理归纳CP临床研究的方向和热点,旨在为今后CP临床研究的设计拓展新思路.

基于ClinicalTrials.gov数据库的子宫内膜异位症临床研究多维度分析

目的:基于ClinicalTrials.gov数据库对子宫内膜异位症的临床研究特点进行多维度分析,为研究者、临床医师和临床药师提供全面和客观的信息参考。方法:全面检索建库以来至2023年10月20日在ClinicalTrials.gov平台注册的子宫内膜异位症临床试验研究,提取相关试验数据,采用文献计量学及对比研究的方法进行统计分析。结果:全球子宫内膜异位症临床研究注册数量共667项,呈逐年增长趋势;美国(127项)、法国(70项)和意大利(57项)的临床试验注册数量最多;试验类型以干预性研究为主(416项,62.4%),其次是观察性研究(251项,37.6%)。在干预性研究中药物治疗有223项(53.6%),为主要干预方式。尽管子宫内膜异位症为女性疾病,但男性受试者亦被纳入考虑范围,其中受试者要求为男性的临床试验有6项,不限性别的临床试验有37项。公司/企业是主要的经费来源,而公共和政府机构的资助相对较少。结论:子宫内膜异位症临床试验研究的发展呈上升阶段,治疗方式以药物治疗为主,但仍存在公共资金和政府机构的投入和关注相对不足的问题。

Adipose-derived stem cells in diabetic foot care:Bridging clinical trials and practical application

Diabetic foot ulcers(DFUs)pose a critical medical challenge,significantly impairing the quality of life of patients.Adipose-derived stem cells(ADSCs)have been identified as a promising therapeutic approach for improving wound healing in DFUs.Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU,its clinical applications remain elusive.In this review,we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs.The review begins with a discussion of the classification and clinical management of diabetic foot conditions.It then discusses the current landscape of clinical trials,focusing on their geographic distribution,reported efficacy,safety profiles,treatment timing,administration techniques,and dosing considerations.Finally,the review discusses the preclinical strategies to enhance ADSC efficacy.This review shows that many trials exhibit biases in study design,unclear inclusion criteria,and intervention protocols.In conclusion,this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches,with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

基于ClinicalTrials.gov和ChiCTR数据库对牙体牙髓病的临床试验注册特点分析

目的汇总注册于美国ClinicalTrials.gov和中国临床研究注册中心(Chinese Clinical Trial Registry,ChiCTR)的牙体牙髓病临床注册资料,分析牙体牙髓病临床试验的注册特征。方法通过检索2000年1月1日至2023年8月20日期间在两个数据库中注册的牙体牙髓病临床研究,提取并分析牙体牙髓病相关临床研究的信息,提取的内容包括注册地区、注册年度、试验题目、研究方向、样本量、试验进展、研究类型、试验设计、盲法、临床试验分期和参与机构名称等信息。结果两个数据库中临床研究的总注册数为536191项,其中牙体牙髓病的临床研究共634项;涉及到43个国家,排名前三的分别是埃及(188项)、中国(130项)和美国(46项);2015年开始牙体牙髓病临床研究注册数量显著增加;研究方向以牙髓病(434项)、龋病(106项),根尖周病(77项)为主,内容主要涉及到病因学、药物干预、外科干预、新技术、新材料等方面;临床试验样本量<100例的临床研究有430项(67.82%),样本量为100~999例的有185项(29.18%);注册时的研究进展状态为已完成试验的项目数最多,有286项(45.11%),其次是未知项(125项)、招募中(110项)、尚未招募(81项);研究类型主要是干预性研究546项,占86.12%,以随机平行对照设计方式为主要设计模式(473项,74.61%);研究设计类型中使用盲法的有423项(66.72%),其中以双盲为主(195项),其次是其他/未注明情况(123项,19.40%),开放性研究(88项,13.88%);临床分期中标记为其他/未标记的项目数量最多(388项),其次是Ⅱ期研究(69项)和初步研究(62项)。临床研究参与机构数量<3的有611项(96.37%),参与机构数量≥3的有23项(3.63%)。结论牙体牙髓病的临床试验注册数量总体呈上升趋势,但仍旧偏少,研究设计的质量有待加强,临床分期的注册信息的完整性有待提高,且多中心临床研究数量较少。今后应充分开展高质量、多中心的临床研究,实现成果的转化。

基于ClinicalTrials数据库分析抗凝血药妊娠期相关临床试验注册及方法学设计特点

目的:针对ClinicalTrials临床试验注册平台,探讨抗凝血药妊娠期应用相关临床试验注册及方法学设计特点。方法:依据抗凝血药及妊娠相关关键词,通过对ClinicalTrials临床试验注册平台进行检索,对题目及干预措施进行初选,根据注册内容进行筛选并提取相关信息,分析注册数量、研究阶段、国家/地区、研究类型等注册特点,评估涉及药物种类、妊娠相关疾病、观察结局、盲法、样本量等方法学设计特点。结果:通过双人检索及筛选,最终纳入109项抗凝血药妊娠期相关研究,我国共涉及19项相关研究。研究设计中以干预性研究为主,同时平行对照研究的研究目的以应用抗凝血药预防及治疗血栓性疾病为主。有50项研究应用盲法,以针对研究者及患者设盲较多。阿司匹林、肝素及低分子肝素涉及的研究分别有70、50项,涉及疾病中妊娠期高血压疾病及子痫、复发性流产、血栓类疾病的研究数量居前3位。已完成的临床研究中,平均样本量、时间跨度分别为780例、3.9年,终止、撤回及暂停的研究分析凸显了前期实验性研究及中期评估对于研究的重要性。结论:通过对ClinicalTrials平台临床研究特点及方法学设计进行分析,能够有效针对我国抗凝血药妊娠期临床试验设计及管理提供借鉴及参考。

基于ClinicalTrials.gov数据库分析骨肉瘤临床试验注册现状

目的 分析全球骨肉瘤临床试验注册情况,了解该领域研究现状和发展态势,为骨肉瘤研究和临床诊治提供新的信息。方法 通过采集2001—2021年期间在美国ClinicalTrials.gov注册平台注册的骨肉瘤临床试验数据,从区域分布、年度趋势、试验进展、研究类型、临床分期、参与机构数量等进行多方面的统计分析。结果 2001—2021年间,全球骨肉瘤临床试验共注册514项,主要集中在北美洲和欧洲;其中干预性临床试验有416项(80.9%),药物相关治疗占87.0%(362/416),抗肿瘤药物研究有127种;显示已完成干预性临床试验仅147项(35.3%),其中已发表论文71项(48.3%),公布试验结果 33项(46.5%)。与2001—2011年相比,2012—2021年间在亚洲地区注册的骨肉瘤干预性临床试验比例从6.1%(10/163)增加到15.0%(38/253),招募前注册从1.2%(2/163)增加到43.9%(111/253),但Ⅱ期临床试验数量在这2个时间段依旧占比最大,分别为46.0%(75/163)和37.9%(96/253)。结论 全球大多数骨肉瘤研究为干预性临床试验,主要集中在药物相关治疗,抗肿瘤药物仍然是骨肉瘤药物干预研究的首选。亚洲地区注册的干预性临床试验较之前明显增加,但研究质量和数量与北美洲、欧洲地区差异仍较大。

帕金森病步态异常非药物康复循证研究:基于ClinicalTrials.gov数据库分析

目的了解非药物疗法治疗帕金森病步态异常的相关临床试验进展。方法检索临床试验注册平台ClinicalTrials.gov建库至2022年10月25日注册的有关非药物疗法治疗帕金森病步态异常的临床试验。两名研究人员独立对试验进行筛选,收集相关信息并对数据根据PICOS原则进行分析,包括注册时间、注册数量、样本量、干预措施、主要结局指标、研究设计等。结果最终纳入临床试验218项。近年来该领域临床试验注册数呈上升趋势。大部分临床试验的样本量<100例(93.6%),主要为21~30例。主要干预措施为神经调控技术,虚拟现实技术、机器人辅助训练技术也逐渐被采用。主要结局指标为评定量表、评定问卷和运动测试。试验设计以随机平行对照试验为主(111项,50.9%)。结论非药物疗法治疗帕金森病步态异常的临床试验注册数逐年增加,随着科学技术的发展,虚拟现实技术、机器人辅助训练技术等新的治疗方法可能成为研究主流。

Applications and safety of gold nanoparticles as therapeutic devices in clinical trials

Use of gold nanoparticles(GNPs)in medicine is an emerging field of translational research with vast clinical implications and exciting therapeutic potential.However,the safety of using GNPs in human subjects is an important question that remains unanswered.This study reviews over 20 clinical trials focused on GNP safety and aims to summarize all the clinical studies,completed and ongoing,to identify whether GNPs are safe to use in humans as a therapeutic platform.In these studies,GNPs were implemented as drug delivery devices,for photothermal therapy,and utilized for their intrinsic therapeutic effects by various routes of delivery.These studies revealed no major safety concerns with the use of GNPs;however,the number of trials and total patient number remains limited.Multi-dose,multicenter blinded trials are required to deepen our understanding of the use of GNPs in clinical settings to facilitate translation of this novel,multifaceted therapeutic device.Expanding clinical trials will require collaboration between clinicians,scientists,and biotechnology companies.