Analysis of the Current Situation of Drug Clinical Trial Institutions in Shaanxi Province

To understand the current situation of institutional registration in Shaanxi Province after the implementation ofregistration system management in drug clinical trial institutions.Relevant information was collected on the“Announcement on the Accreditation of Drug Clinical Trial Institutions”issued by the National Medical Products Administration from 2005 to August 2022,the record management information system of drug and medical device clinical trial institutions,and the drug clinical trial registration and information publicity platform.A retrospective analysis was carried out in terms of institutional development,regional distribution,registered majors,principal investigators,and the number of drug clinical trials.After the implementation of institution registration,the number of drug clinical trial institutions in Shaanxi Province increased by 47.4%,884 principal investigators were registered,the number of registered majors expanded from 58 qualified to 117,and the professional scope increased by 50.4%.The policy of institution registration is conducive to promoting the rational use of medical resources and the development of drug clinical trial institutions and improving the healthy development of the pharmaceutical industry in Shaanxi Province.

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。

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.

The Role of Study Nurses in Clinical Trials of IBD Drugs

Objective: To explore the establishment and roles of study nurses in IBD drug clinical trials. Methods: The management experience of this department’s study nurses in IBD drug clinical trials was retrospectively analyzed. Results: The study nurses played very important roles at all links during the preliminary preparation of IBD drug clinical trials, the whole-process management after project initiation, and the later work of project conclusion. Conclusions: As direct participants in drug clinical trials, study nurses play a very important role in ensuring standardization of the trial process, safeguarding patient’s rights and safety, and assisting investigators in carrying out study works smoothly.

Xi-Feng-Hua-Shi granules for diarrhea-predominant irritable bowel syndrome:protocol for a randomized,double-blind,placebo-controlled multi-center clinical trial

Background:Irritable bowel syndrome(IBS)is a common functional bowel disorder that can severely affect the quality of life of patients.Limited drugs have been reported for modern medical IBS treatment.The advantages of traditional Chinese medicine(TCM)treatment are gradually becoming prominent.Xi-Feng-Hua-Shi granules have been clinically used for diarrhea-predominant IBS(IBS-D)treatment for many years in TCM practice.Thus,this study aimed to further verify the effectiveness and safety of Xi-Feng-Hua-Shi(XFHS)granules in IBS-D treatment through a randomized,double-blind,placebo-controlled multi-center clinical trial and provide high-quality evidence for its effectiveness and safety in treatment,as well as provide a basis for clinical rational drug use and explore new clinical IBS-D treatment plans.Methods:A randomized,double-blind,placebo-controlled multi-center clinical trial will be performed in 23 hospitals.A total of 300 participants will be randomly divided into the experimental group(prescribed with XFHS granules)and the control group(prescribed with the placebo granules),with 150 participants in each group.The appearance,shape,color,and taste of the placebo granules are the same as those of XFHS granules.All participants will receive a 4-week treatment and a 6-month follow-up.The primary outcome is the overall clinical efficacy;the secondary outcomes are the IBS-Symptom Severity Score(IBS-SSS),TCM Syndrome Evaluation,and the IBS-Quality of Life(IBS-QoL)score,mental state assessment,and recurrence rate.Outcome measures(including primary and secondary outcome measures)are collected at baseline,as well as 2,4,16,and 28 weeks post-intervention.Discussion:This randomized,placebo-controlled,multi-center trial may provide high-quality evidence for the clinical XFHS granule efficacy in IBS-D treatment.Additionally,this study will conduct safety evaluations to provide a basis for clinical rational drug use.

基于Clinicaltrials.gov平台的口腔鳞状细胞癌临床研究注册特点分析

目的:基于Clinicaltrials.gov平台分析全球口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的临床研究注册特点,了解研究现状和发展趋势,为OSCC临床研究和诊疗提供新思路。方法:通过挖掘Clinicaltrials.gov平台建库至2023年3月24日已注册的OSCC临床试验数据,从年度趋势、地域分布、临床分期、研究类型、受试者人数、经费来源、机构数量等多方面进行统计分析,归纳其临床研究特征。结果:共纳入OSCC临床注册研究332项,注册数量最多的3个国家是美国(188项,56.63%),中国(37项,11.14%)和法国(18项,5.42%)。332项研究中干预性研究和观察性研究分别占83.43%和16.57%,277项干预性试验中药物干预204项(73.65%),其中单克隆抗体药物研究79项(28.52%),顺铂60项(21.66%)。119项平行试验中105项(88.24%)采用随机方法,44项(36.97%)为盲法。332项研究中约1/3(111项,33.43%)归属于Ⅱ期临床试验,受试者人数在50以下的占比超过一半(177项,53.31%)。结论:OSCC的临床研究存在地区不均衡性,多中心大样本随机三盲对照的高质量临床研究不足,应加强临床试验注册的培训和审查,以促进OSCC临床试验高质量的开展,推动其治疗方案的优化。

Quality Management Model for Phase I Clinical Drug Trials:A Structural Equation Model

This study aimed to construct a quality management model for phase I clinical drug trials.A cross-sectional survey was conducted and data were collected from 604 respondents at 69 institutions in China engaged in phase I clinical drug trials.Exploratory and confirmatory factor analyses were used to develop the survey tool.Structural equation modeling was used to construct a quality management model for phase I clinical drug trials.The results showed that the final survey tool had good reliability and validity(Cronbach’sα=0.938,root mean square error of approximation=0.074,comparative fit index=0.962,and Tucker—Lewis index=0.955).The model included five dimensions:government regulation,industry management,medical institution management,research team management,and contract research organization(CRO)management.In total,22 measurement items were obtained.The structural equation model indicated government regulation,industry management,medical institution management,and CRO management significantly affected the quality of phase I clinical drug trials(β=0.195,β=0.331,β=0.279,andβ=−0.267,respectively;P<0.05).Research team management had no effect on the quality of trials(β=0.041,P=0.610).In conclusion,the model is valuable for identifying factors influencing phase I clinical drug trials and guiding quality management practices.

Regulation of Drug Clinical Trials in China: Course and Development Trend

Objective To provide a basis for future regulation reform of drug clinical trials in China in the context of the continuous deepening of drug regulation reform. Methods Literature review and regulation study were conducted to analyze the course and development trend of drug clinical trial regulation in China. Results and Conclusion It is found that the regulation system and the standardization for clinical trials in China are gradually improving, but there is still a gap compared with developed countries. In the future, the regulation authorities still need to further improve relevant regulations, clarify regulation responsibilities, and to improve the drug clinical trial review system to ensure the quality of clinical trials and the safety and effectiveness of listed drugs.

The Expanding Roles of Hospital Pharmacists in Clinical Drug Trials in China

Objective To aim at summarizing the role of hospital pharmacists in clinical drug trials in China against the background that hospital pharmacists have already involved in team-based patient care.Methods The roles and responsibilities of Chinese hospital pharmacists were listed and categorized.Results and Conclusion There has been an upsurge in clinical drug trials in China.Hospital pharmacists play increasingly important roles in all aspects of clinical trials,such as stakeholder liaisons,protocol developers,ethics committee members,research team members,study drug managers,and subject intervention agents.Hospital pharmacists are an integral part of a clinical drug trial multidisciplinary team.Their value is reflected in several pharmacist-led or pharmacist-participating clinical trials as well as the trial project management position within hospitals.Pharmacists should be the designers,researchers,managers and supervisors of clinical drug trials.We expect that all clinical trial projects will include hospital pharmacists in their research teams soon.

Anti-obesity drugs currently used and new compounds in clinical development

Obesity is a chronic disease which requires treatment. As lifestyle interventions alone hardly ever result in long-term weight loss, pharmacotherapy is an impor-tant adjunct to lifestyle measures to improve the induc-tion and maintenance of weight loss. Owing to the lim-ited options currently available for the pharmacological treatment of obesity, it is imperative to develop new safe compounds. This study aims to review the current medications approved by European Medicines Agency and United States Food and Drug Administration （FDA） for the treatment of obesity, focusing essentially on their benefits and risks, as well as on the new drugs which are presently under clinical trials. Moreover, it lists the anti-obesity agents that have been recently withdrawn from the market. A revision of the scientifc literature was carried out, through a search on Pubmedfor papers published from January 2010 to January2013. Orlistat （Xenical？） is currently the only long-termpharmacotherapy for obesity available in the Europeanmarket, as rimonabant and sibutramine were with-drawn in 2008 and 2010, respectively, due to serious psychiatric and cardiovascular adverse effects. Lorca-serin （Belviq？） and the association of phentermine and topiramate （QsymiaTM） were recently approved by FDA. Orlistat suppresses appetite inhibiting gastrointestinal lipase, being its adverse effects mostly gastrointestinal. Lorcaserin activates 5-HT2C receptors, phentermine is a norepinephrine releasing drug, and topiramate is an anticonvulsivant drug with weight loss properties.

Clinical Trial Phases

Developers of drugs, biologicals, and medical devices must ensure product safety, demonstrate medical benefit in people, and mass produce the product. Preclinical development starts before clinical trials and the main goals are to determine safety and effectiveness of the intervention. If preclinical studies show that the therapy is safe and effective, clinical trials are started. Clinical trial phases are steps in the research to determine if an intervention would be beneficial or detrimental to humans and include Phases 0, I, II, III, IV, and V clinical studies. Understanding the basis of clinical trial phases will help researchers plan and implement clinical study protocols and, by doing so, improve the number of therapies coming to market for patients.

Design flaws in randomized, placebo controlled, double blind clinical trials

The hypothesis in drug clinical trials is that the drug is better than a placebo in patients suffering from a disease. The unstated assumption is that the drug cures the disease or is a powerful treatment for the disease. This is an incorrect assumption. Drugs do not cure or treat diseases. The body heals itself; drugs promote this ability of the body to heal itself. Placebos are assumed to be inactive; however, placebos can also promote the ability of the body to heal itself. Placebos are actually treatments that can stimulate endogenous healing mechanisms. The possible place of placebos in health management is controversial. Clinical trial design should be altered. The hypothesis of clinical trials should be that the drug speeds up or improves the healing of the patient, putting patient healing as the first objective. Placebos should not be used as controls but could be tested as drugs in their own right. The control in clinical trials should be no treatment. Alternatively, new drugs could be compared to existing drugs in clinical trials.

Clinical Trial Participant Willingness and Influencing Factors Study of Patients with Inflammatory Bowel Disease

Objective: The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. Method: An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. Result: Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. Conclusion: The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.

Randomized,blind,parallel-controlled and multiple-centre clinical trial on the efficacy and safety of sustained-released leuprolide acetate in the treatment of endometriosis

Objective:To evaluate the efficacy and safety of leuprolide acetate in the treatment of endometriosis. Methods:The patients with endometriosis were randomly divided into leuprolide(n = 75) and control(n=74) groups.They were treated with either sustained-release injection of leuprolide acetate or Enatntone injection(control) for 3 times totally.After treatment,the ovarian mass volume was measured under B ultrasound.The changes in hormone levels of estrodial(E_2),FSH and LH,the pelvic signs,the scores of the patient's subjective symptoms during menstruation and non-menstrual days were observed. Results:The rate of changes in ovarian mass volume had no statistically significant difference between the two groups(P=0.495-0.965).The average reduction of ovarian mass volume was 47.91%in leuprolide group,and 53.51%in the control group 12 weeks after first medication.The distinct improvement rate and improvement rate of total symptom scores during menstruation and non-menstrual days had no significant difference between the two groups.The hormone levels of E_2,FSH and LH were not significantly different between the two groups.The differences in the incidence of adverse reactions were not significant between the two groups. Conclusion:Leuprolide acetate produced by Livzon China is effective and safe in the treatment of endometriosis.

Treatment‐related adverse events of antibody‐drug conjugates in clinical trials:A systematic review and meta‐analysis

Background:The wide use of antibody‐drug conjugates(ADCs)is transforming the cancer‐treatment landscape.Understanding the treatment‐related adverse events(AEs)of ADCs is crucial for their clinical application.We conducted a meta‐analysis to analyze the profile and incidence of AEs related to ADC use in the treatment of solid tumors and hematological malignancies.Methods:We searched the PubMed,Embase,and Cochrane Library databases for articles published from January 2001 to October 2022.The overall profile and incidence of all‐grade and grade≥3 treatment‐related AEs were the primary outcomes of the analysis.Results:A total of 138 trials involving 15,473 patients were included in this study.The overall incidence of any‐grade treatment‐related AEs was 100.0%(95%confidence interval[CI]:99.9%–100.0%;I2=89%)and the incidence of grade≥3 treatment‐related AEs was 6.2%(95%CI:3.0%–12.4%;I2=99%).Conclusions:This study provides a comprehensive overview of AEs related to ADCs used for cancer treatment.ADC use resulted in a high incidence of any‐grade AEs but a low incidence of grade≥3 AEs.The AE profiles and incidence differed according to cancer type,ADC type,and ADC components.

COVID-19 therapeutics:Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)causes the compli-cated disease COVID-19.Clinicians are continuously facing huge problems in the treatment of patients,as COVID-19-specific drugs are not available,hence the principle of drug repurpos-ing serves as a one-and-only hope.Globally,the repurposing of many drugs is underway;few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials.Here in this review,our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs,the potential mechanism of actions,and the current clinical trial status of various drugs which are under repurposing since early 2020.At last,we briefly proposed the probable phar-macological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.

Psychedelic Drug Therapy for Mental Disorders?

Objective: Psychedelic drug therapy is banned in all countries of the world except Australia, where the government regulatory watchdog, the Therapeutic Goods Administration, is planning to allow approved psychiatrists, as of July 1, 2023, to prescribe psilocybin to treat depression and MDMA to treat post-traumatic stress disorder, a move precipitated by the U.S. Food and Drug Administration’s designation of these two drugs as “breakthrough therapy”. The objective of the present article is to demonstrate that the evidence on which the FDA and then the TGA relied is irretrievably flawed and should be dismissed. Method: Expert review of psychedelic therapy clinical trials and specifically of the methodology and measures used. Results: The present review demonstrates that the studies the U.S. FDA and the Australian TGA relied on to approve these two psychedelic drugs for therapy are irretrievably flawed. All future trials will follow the same procedure and are therefore bound to be flawed as well. Conclusions: Psychedelic drug studies have so far provided no trustworthy evidence of their effectiveness for treating mental disorders and are not likely to produce this evidence in the future. Psychedelic drug therapy is in any event impractical because of its specialized training requirements and very high treatment costs. It is also dangerous because false publicity about its effectiveness will almost certainly lead to unsupervised self-dosing with drugs that not only are illegal but have an unacceptably high addiction rate.

基于OBE理念的药物临床试验课程教学改革研究

首都医科大学将成果导向型教学(OBE)理念引入药物临床试验课程教学改革中。教师针对课程教学内容更新速度快、教学方式传统陈旧、考评模式较为单一等普遍存在的问题,以学生为中心组织和引导教学过程,优化教学大纲、改善教学方法、提升自身教学能力、完善学生评价体系,有效提升了教学产出和学生的创新性学习能力,可为相关课程教学改革提供借鉴。

药物临床试验培训导入临床药学教学的分析与思考

基于国家大健康产业、医药产业创新发展对临床药学和临床试验人才数量和质量的新需求,初步探讨在临床药学人才教学中导入药物临床试验相关理论、实践的必要性和方式。依据院校临床药学培养教学内容和特点,将临床试验相关理论和实践整合到临床药学培养的不同阶段开展教学,在临床药学基础理论教学中导入药物临床试验理论和案例教学,在临床药学毕业实践中进行临床试验实践教学提升能力,在临床药学研究生培养阶段进行临床试验创新培养。一方面提高临床药学专业学生实践能力,扩大临床试验人才培养路径;另一方面提升临床药学学生的创新思维和能力,满足社会大健康产业多元需求。

广东省药物临床试验机构备案情况及监管现状分析

目的:了解广东省药物临床试验机构备案形势、临床试验开展情况和临床试验机构监管现状,为监管相关工作提供参考。方法:从药物临床试验机构备案管理信息系统提取药物临床试验机构备案信息,通过电子调查问卷收集药物临床试验项目数量,梳理汇总药物临床试验机构监督检查情况,并从多个维度统计分析相关数据。结果:截至2023年12月31日,广东省共备案140家药物临床试验机构,主要为三级甲等公立医院,累计备案118个专业。备案药物临床试验机构分布于19个地级市,其中位于广州市的药物临床试验机构(占比32%)承接了广东省78%的药物临床试验。监督检查中发现一些机构在组织管理、责任意识和伦理审查方面尚存在问题,新备案机构尤为突出。结论:药物临床试验机构备案制的施行促进了广东省药物临床试验资源的释放,但凸显了技术层次不齐、专业布局不合理和区域发展不均衡等制约资源有效利用的问题。建议监管部门从加强指导服务力度方面完善监管机制,助力提升药物临床试验资源的利用效率,进而推动广东省药物临床试验机构健康发展。