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 disea...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.展开更多
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 memb...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.展开更多
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 nur...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.展开更多
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...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.展开更多
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 sim...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.展开更多
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 o...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。展开更多
Enrolling in clinical trials could be time-sensitive and time-demanding tasks for the research site, especially if it is a private research organization compared to the research conducted at an academic or medical cen...Enrolling in clinical trials could be time-sensitive and time-demanding tasks for the research site, especially if it is a private research organization compared to the research conducted at an academic or medical center. Every study differs in various aspects, such as phases, study indication, eligibility criteria, etc. In terms of meeting the enrollment deadline, typically, the study indication and availability of the patient’s population at the geographical area of the research site would decide if the trial could be time-consuming. Patient recruitment and retention are critical for the success of every clinical trial;however, worldwide, this area is facing tremendous pressure and challenges. Globally 55% of clinical trials terminated due to low recruitment, with an average enrollment success rate of 40% for Phase III and IV trials. Over 80% of clinical trial attempts fail to enroll, extending the study and adding new study sites. In the United States, more than 80% of clinical trials fail to achieve targeted patient enrollment, and 30% of study participants discontinue participation. This article reviewed various factors hindering clinical trial recruitment and retention and suggested strategies to make the research site successful.展开更多
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 imp...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.展开更多
Objective:This report presents an overview on the progress of clinical trials in Indonesia based on database assessment from clinical trial registries.Methods:Study records that were registered up to December 26,2018,...Objective:This report presents an overview on the progress of clinical trials in Indonesia based on database assessment from clinical trial registries.Methods:Study records that were registered up to December 26,2018,were extracted from three clinical trial registries(ClinicalTrials.gov,ISRCTN registry,and EudraCT)and a clinical trial register(WHO International Clinical Trials Registry Platform(ICTRP))with the keyword“Indonesia”.A total of 505 records comprised of 402 interventional studies and 103 observational studies were found and analyzed.Results:The top five noncommunicable diseases(NCDs)studied were cancers,diabetes,cardiac diseases,hypertension,and gastrointestinal diseases,while the top five infectious diseases(IDs)were malaria,tuberculosis,vaccines for IDs,HIV,and dengue.Remarkably,the proportion of regional studies(within Indonesia only)was higher than that of multiregional studies(including areas outside of Indonesia)in general.This trend became most apparent after the issuance of national regulations on Material Transfer Agreements(MTA)and other rules.Upon closer scrutiny,regional clinical trials and multiregional clinical trials(MRCTs)in Indonesia differed in terms of sponsorship,target population and size,interventions,and study phases.Conclusions:The total number of clinical trials in Indonesia is increasing and is mainly attributed to the growing number of regional clinical trials sponsored from within the country.Interrelated factors have shaped the characteristics of these as compared to the dwindling number of MRCTs.Establishment of a national level of management is an option that can better facilitate both MRCTs as well as regional clinical trials,to better address the national health issues,and to cope with the regulations.展开更多
Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenc...Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.展开更多
Cerebral palsy is the most common disease in children associated with lifelong disability in many countries.Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone c...Cerebral palsy is the most common disease in children associated with lifelong disability in many countries.Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral palsy.Stem cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem cells.In this review, we summarize the design schemes and results of these clinical trials.Our findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical trials.Furthermore, we also assess the safety and efficacy of these clinical trials.We anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.展开更多
Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia...Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia mulberry leaf is used as tea to complement the treatment of diabetes mellitus.The methods by which mulberry leaf affects the body and its mechanism when combined with chemical agents have been studied extensively.Conclusions:We summarize the possible mechanisms of the anti-diabetic effects of mulberry leaf based on extraction procedures,in vitro and in vivo experiments,and clinical trials.We also discuss the hypothesis that crosstalk and“critical nodes”may be useful for a deeper molecular understanding of the treatment and prevention of diabetes with mulberry leaf.展开更多
Infections or virus-based diseases are a significant threat to human societies and could affect the whole world within a very short time-span.Corona Virus Disease-2019(COVID-19),also known as novel coronavirus or SARS...Infections or virus-based diseases are a significant threat to human societies and could affect the whole world within a very short time-span.Corona Virus Disease-2019(COVID-19),also known as novel coronavirus or SARSCoV-2(Severe Acute Respiratory Syndrome-Coronavirus-2),is a respiratory based touch contiguous disease.The catastrophic situation resulting from the COVID-19 pandemic posed a serious threat to societies globally.The whole world is making tremendous efforts to combat this life-threatening disease.For taking remedial action and planning preventive measures on time,there is an urgent need for efficient prediction models to confront the COVID-19 outbreak.A deep learning-based ARIMA-LSTM hybrid model is proposed in this article for predicting the COVID-19 outbreak by utilizing real-time information from the WHO’s daily bulletin report as well as provides information regarding clinical trials across the world.To evaluate the suitability and performance of our proposed model compared to other well-established prediction models,an experimental study has been performed.To estimate the prediction results,the three performance measures,i.e.,Root Mean Square Error(RMSE),Coefficient of determination(R2 Score),and Mean Absolute Percentage Error(MAPE)have been employed.The prediction results of fifty countries substantiated the fact that the proposed ARIMA-LSTM hybrid model performs very well as compared to other models.The proposed model archives the lowest RMSE,lowest MAPE,and highest R2 Score throughout the testing,under varied selection criteria(country-wise).This article aims to contribute a deep learning-based solution for the wellbeing of livings and to provide the current status of clinical trials across the globe.展开更多
Hepatocellular carcinoma(HCC)is a leading cause of cancer-associated mortality worldwide.HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers.Advanced HCC is manag...Hepatocellular carcinoma(HCC)is a leading cause of cancer-associated mortality worldwide.HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers.Advanced HCC is managed with systemic therapies;the tyrosine kinase inhibitor(TKI)sorafenib has been used in 1st-line setting since 2007.Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors(ICIs)are licensed in 1st-and 2nd-line treatment setting.The treatment field of advanced HCC is continuously evolving.Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents,such as other ICIs,TKIs,and anti-angiogenics.Novel immunotherapies including adoptive cell transfer,vaccine-based approaches,and virotherapy are also being brought to the fore.Yet,despite advances,several challenges persist.Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort.Consequently,issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications,comorbidities,or poor performance status;lack of response,efficacy,and safety data;and cost-effectiveness.Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making.This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC,with a focus on ICIs,as well as novel immunotherapy strategies underway.展开更多
Objective:To characterize otologic clinical trials and examine otologic clinical trial trends from 2008 to 2018 using the clinicaltrials.gov database.Methods:Data was collected from clinicaltrials.gov and included all...Objective:To characterize otologic clinical trials and examine otologic clinical trial trends from 2008 to 2018 using the clinicaltrials.gov database.Methods:Data was collected from clinicaltrials.gov and included all clinical trials that focused on otology from 2008 to 2018.Outcome measures include status of trials,funding sources,details regarding otologic conditions studied,and trends in clinical trials.Results:There were 992 otology clinical trials from 2008 to 2018.457(46.1%)were completed and 94(9.5%)were discontinued.Industry remained the highest(76.5%)contributor to otology clinical trials.The otologic conditions studied,from most common to least common,include hearing loss(40.6%),vestibulopathy(18.8%),tinnitus(18.8%),and otitis media(15.1%).The number of otology clinical trials increased by an average of 12.0 trials per year from 2008 to 2018(p<0.001).The number of otology clinical trials focusing on hearing loss and vestibulopathy significantly increased over the studied period(p<0.001),while those focusing on tinnitus and otitis media did not(p=0.09 and p=0.20,respectively).The majority of clinical trials on each of these four conditions focused on treatment options.Conclusion:Our study describes trends in otology clinical trials registered on clinicaltrials.gov from 2008 through 2018.The total number of clinical trials over this time period increased significantly,driven by trials investigating hearing loss and vestibulopathy.Furthermore,most clinical trials were industrysponsored and focused on treatment modalities.Our study provides an outline of otology clinical trials registered in a US web-based database,which may be of use for the development of future clinical trials.展开更多
It is evident that both recruitment and retention play critical roles in clinical trials. Recruitment and retention models are beginning to be analyzed worldwide in an effort to assess how to conduct studies more effi...It is evident that both recruitment and retention play critical roles in clinical trials. Recruitment and retention models are beginning to be analyzed worldwide in an effort to assess how to conduct studies more efficiently, all the while, allowing researchers to provide sound and ethical data to help advance medicine through clinical studies. Sponsors and sites have recognized that clinical trial enrollment must become more diverse and inclusive. In this review, we address the important topics of recruitment and retention in clinical trials. Specifically, the obstacles in regard to recruiting vulnerable populations. Methodologies to improve both the understanding of the study population and community engagement are outlined. In particular, newer strategies such as use of social media and more reliable strategies such as trust and relationship building are described in detail. A strong focus on recruitment is becoming widely recognized as being of such importance that consideration is given to this key component even during initial protocol development. Attention to recruitment and retention in the strategic planning process of clinical trials can mitigate enrollment issues that clinical researchers are experiencing.展开更多
Objectives: Our aim was to clarify the study characteristics of countries that have registered clinical trials studies and to calculate the percentage of clinical trials that were registered in each country’s registr...Objectives: Our aim was to clarify the study characteristics of countries that have registered clinical trials studies and to calculate the percentage of clinical trials that were registered in each country’s registry, and try to find and evaluate the factors determining that percentage. Design and Methods: The present study is a cross-sectional study using data from clinical trials registered from January 1, 2011, to December 31, 2015. Only countries with more than 2000 registered trials were included for further study. Ten countries met that criterion: United States, Japan, Iran, Australia, New Zealand, China, India, Germany, United Kingdom, and Netherland. The percentage of clinical trials that were registered in each country’s registry was calculated, and the factors determining that percentage were sought and analyzed through an exploratory approach. Results: The chi-squared test of independence indicated that the rate of clinical trial registration significantly differed between countries. From the adjusted standardized residuals, the percentage of clinical trials that were registered in the country of origin was higher in the United States, India, Japan, and Australia/New Zealand than in the European Union and China. Conclusion: The United States requires that informed consent documents for clinical trials contain clinical trial registration numbers from ClinicalTrials.gov, which could be the reason for the extremely high percentage of registered clinical trials (94%). Since the European Union does not have this requirement, clinical trials conducted in the European Union do not have to be registered in the countries in which they are conducted.展开更多
The effectiveness of medical interventions should be based on the results of all properly conducted clinical trials, whether or not the trials have been published. The results of unpublished trials are systematically ...The effectiveness of medical interventions should be based on the results of all properly conducted clinical trials, whether or not the trials have been published. The results of unpublished trials are systematically different from those that are published; they tend to be "negative" (find no effect or harm) or fail to support the interests of the funding agency. Therefore, relying on published trials alone can provide a biased view of effectiveness and safety. Registration of clinical trials at their inception, in widely available registries, makes it possible for all stakehold-展开更多
文摘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.
基金Supported by the Science and Technology Program of Guangzhou(No.201803010066)the High-level Hospital Construction Project,Zhongshan Ophthalmic Center,Sun Yat-sen University(No.303010202).
文摘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.
文摘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.
文摘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.
基金supported by the Special Foundation of Research Institute of Drug Regulatory Science,Shenyang Pharmaceutical University(2021jgkx004).
文摘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.
基金the Japan Agency for Medical Research and Development(Grant Nos.20lk0201002j0001,21lk0201005j0001,and 22lk0201007j0001)。
文摘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。
文摘Enrolling in clinical trials could be time-sensitive and time-demanding tasks for the research site, especially if it is a private research organization compared to the research conducted at an academic or medical center. Every study differs in various aspects, such as phases, study indication, eligibility criteria, etc. In terms of meeting the enrollment deadline, typically, the study indication and availability of the patient’s population at the geographical area of the research site would decide if the trial could be time-consuming. Patient recruitment and retention are critical for the success of every clinical trial;however, worldwide, this area is facing tremendous pressure and challenges. Globally 55% of clinical trials terminated due to low recruitment, with an average enrollment success rate of 40% for Phase III and IV trials. Over 80% of clinical trial attempts fail to enroll, extending the study and adding new study sites. In the United States, more than 80% of clinical trials fail to achieve targeted patient enrollment, and 30% of study participants discontinue participation. This article reviewed various factors hindering clinical trial recruitment and retention and suggested strategies to make the research site successful.
基金supported by grants from Canadian Institutes of Health Research(Grant Nos.:MOP-42546,MOP-119514,PJT148847).
文摘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.
文摘Objective:This report presents an overview on the progress of clinical trials in Indonesia based on database assessment from clinical trial registries.Methods:Study records that were registered up to December 26,2018,were extracted from three clinical trial registries(ClinicalTrials.gov,ISRCTN registry,and EudraCT)and a clinical trial register(WHO International Clinical Trials Registry Platform(ICTRP))with the keyword“Indonesia”.A total of 505 records comprised of 402 interventional studies and 103 observational studies were found and analyzed.Results:The top five noncommunicable diseases(NCDs)studied were cancers,diabetes,cardiac diseases,hypertension,and gastrointestinal diseases,while the top five infectious diseases(IDs)were malaria,tuberculosis,vaccines for IDs,HIV,and dengue.Remarkably,the proportion of regional studies(within Indonesia only)was higher than that of multiregional studies(including areas outside of Indonesia)in general.This trend became most apparent after the issuance of national regulations on Material Transfer Agreements(MTA)and other rules.Upon closer scrutiny,regional clinical trials and multiregional clinical trials(MRCTs)in Indonesia differed in terms of sponsorship,target population and size,interventions,and study phases.Conclusions:The total number of clinical trials in Indonesia is increasing and is mainly attributed to the growing number of regional clinical trials sponsored from within the country.Interrelated factors have shaped the characteristics of these as compared to the dwindling number of MRCTs.Establishment of a national level of management is an option that can better facilitate both MRCTs as well as regional clinical trials,to better address the national health issues,and to cope with the regulations.
基金supported by 2019 Scientific Research Project of Traditional Chinese Medicine in Gansu Province of China,No.GZK-2019-46(to XWK and YBL)。
文摘Spinal cord injury can lead to severe motor,sensory and autonomic nervous dysfunctions.However,there is currently no effective treatment for spinal cord injury.Neural stem cells and progenitor cells,bone marrow mesenchymal stem cells,olfactory ensheathing cells,umbilical cord blood stem cells,adipose stem cells,hematopoietic stem cells,oligodendrocyte precursor cells,macrophages and Schwann cells have been studied as potential treatments for spinal cord injury.These treatments were mainly performed in animals.However,subtle changes in sensory function,nerve root movement and pain cannot be fully investigated with animal studies.Although these cell types have shown excellent safety and effectiveness in various animal models,sufficient evidence of efficacy for clinical translation is still lacking.Cell transplantation should be combined with tissue engineering scaffolds,local drug delivery systems,postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life.This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury,with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.
基金supported by the National Natural Science Foundation of China, No.81471308(to JL)the Stem Cell Clinical Research Project of China, No.CMR-20161129-1003(to JL)the Dalian Innovation Technology Funding of China, No.2018 J11 CY025(to JL)。
文摘Cerebral palsy is the most common disease in children associated with lifelong disability in many countries.Clinical research has demonstrated that traditional physiotherapy and rehabilitation therapies cannot alone cure cerebral palsy.Stem cell transplantation is an emerging therapy that has been applied in clinical trials for a variety of neurological diseases because of the regenerative and unlimited proliferative capacity of stem cells.In this review, we summarize the design schemes and results of these clinical trials.Our findings reveal great differences in population characteristics, stem cell types and doses, administration methods, and evaluation methods among the included clinical trials.Furthermore, we also assess the safety and efficacy of these clinical trials.We anticipate that our findings will advance the rational development of clinical trials of stem cell therapy for cerebral palsy and contribute to the clinical application of stem cells.
基金This work was carried out with the support of National Natural Science Foundation(No.81374027),the People’s Republic of China.
文摘Backgrounds:Diabetes mellitus,especially type 2 diabetes,with its fast-rising prevalence,has become a global epidemic.Mulberry(Morus alba L.)leaf has been known to have hypoglycemic effects since ancient times.In Asia mulberry leaf is used as tea to complement the treatment of diabetes mellitus.The methods by which mulberry leaf affects the body and its mechanism when combined with chemical agents have been studied extensively.Conclusions:We summarize the possible mechanisms of the anti-diabetic effects of mulberry leaf based on extraction procedures,in vitro and in vivo experiments,and clinical trials.We also discuss the hypothesis that crosstalk and“critical nodes”may be useful for a deeper molecular understanding of the treatment and prevention of diabetes with mulberry leaf.
文摘Infections or virus-based diseases are a significant threat to human societies and could affect the whole world within a very short time-span.Corona Virus Disease-2019(COVID-19),also known as novel coronavirus or SARSCoV-2(Severe Acute Respiratory Syndrome-Coronavirus-2),is a respiratory based touch contiguous disease.The catastrophic situation resulting from the COVID-19 pandemic posed a serious threat to societies globally.The whole world is making tremendous efforts to combat this life-threatening disease.For taking remedial action and planning preventive measures on time,there is an urgent need for efficient prediction models to confront the COVID-19 outbreak.A deep learning-based ARIMA-LSTM hybrid model is proposed in this article for predicting the COVID-19 outbreak by utilizing real-time information from the WHO’s daily bulletin report as well as provides information regarding clinical trials across the world.To evaluate the suitability and performance of our proposed model compared to other well-established prediction models,an experimental study has been performed.To estimate the prediction results,the three performance measures,i.e.,Root Mean Square Error(RMSE),Coefficient of determination(R2 Score),and Mean Absolute Percentage Error(MAPE)have been employed.The prediction results of fifty countries substantiated the fact that the proposed ARIMA-LSTM hybrid model performs very well as compared to other models.The proposed model archives the lowest RMSE,lowest MAPE,and highest R2 Score throughout the testing,under varied selection criteria(country-wise).This article aims to contribute a deep learning-based solution for the wellbeing of livings and to provide the current status of clinical trials across the globe.
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-associated mortality worldwide.HCC is an inflammation-associated immunogenic cancer that frequently arises in chronically inflamed livers.Advanced HCC is managed with systemic therapies;the tyrosine kinase inhibitor(TKI)sorafenib has been used in 1st-line setting since 2007.Immunotherapies have emerged as promising treatments across solid tumors including HCC for which immune checkpoint inhibitors(ICIs)are licensed in 1st-and 2nd-line treatment setting.The treatment field of advanced HCC is continuously evolving.Several clinical trials are investigating novel ICI candidates as well as new ICI regimens in combination with other therapeutic modalities including systemic agents,such as other ICIs,TKIs,and anti-angiogenics.Novel immunotherapies including adoptive cell transfer,vaccine-based approaches,and virotherapy are also being brought to the fore.Yet,despite advances,several challenges persist.Lack of real-world data on the use of immunotherapy for advanced HCC in patients outside of clinical trials constitutes a main limitation hindering the breadth of application and generalizability of data to this larger and more diverse patient cohort.Consequently,issues encountered in real-world practice include patient ineligibly for immunotherapy because of contraindications,comorbidities,or poor performance status;lack of response,efficacy,and safety data;and cost-effectiveness.Further real-world data from high-quality large prospective cohort studies of immunotherapy in patients with advanced HCC is mandated to aid evidence-based clinical decision-making.This review provides a critical and comprehensive overview of clinical trials and real-world data of immunotherapy for HCC,with a focus on ICIs,as well as novel immunotherapy strategies underway.
文摘Objective:To characterize otologic clinical trials and examine otologic clinical trial trends from 2008 to 2018 using the clinicaltrials.gov database.Methods:Data was collected from clinicaltrials.gov and included all clinical trials that focused on otology from 2008 to 2018.Outcome measures include status of trials,funding sources,details regarding otologic conditions studied,and trends in clinical trials.Results:There were 992 otology clinical trials from 2008 to 2018.457(46.1%)were completed and 94(9.5%)were discontinued.Industry remained the highest(76.5%)contributor to otology clinical trials.The otologic conditions studied,from most common to least common,include hearing loss(40.6%),vestibulopathy(18.8%),tinnitus(18.8%),and otitis media(15.1%).The number of otology clinical trials increased by an average of 12.0 trials per year from 2008 to 2018(p<0.001).The number of otology clinical trials focusing on hearing loss and vestibulopathy significantly increased over the studied period(p<0.001),while those focusing on tinnitus and otitis media did not(p=0.09 and p=0.20,respectively).The majority of clinical trials on each of these four conditions focused on treatment options.Conclusion:Our study describes trends in otology clinical trials registered on clinicaltrials.gov from 2008 through 2018.The total number of clinical trials over this time period increased significantly,driven by trials investigating hearing loss and vestibulopathy.Furthermore,most clinical trials were industrysponsored and focused on treatment modalities.Our study provides an outline of otology clinical trials registered in a US web-based database,which may be of use for the development of future clinical trials.
文摘It is evident that both recruitment and retention play critical roles in clinical trials. Recruitment and retention models are beginning to be analyzed worldwide in an effort to assess how to conduct studies more efficiently, all the while, allowing researchers to provide sound and ethical data to help advance medicine through clinical studies. Sponsors and sites have recognized that clinical trial enrollment must become more diverse and inclusive. In this review, we address the important topics of recruitment and retention in clinical trials. Specifically, the obstacles in regard to recruiting vulnerable populations. Methodologies to improve both the understanding of the study population and community engagement are outlined. In particular, newer strategies such as use of social media and more reliable strategies such as trust and relationship building are described in detail. A strong focus on recruitment is becoming widely recognized as being of such importance that consideration is given to this key component even during initial protocol development. Attention to recruitment and retention in the strategic planning process of clinical trials can mitigate enrollment issues that clinical researchers are experiencing.
文摘Objectives: Our aim was to clarify the study characteristics of countries that have registered clinical trials studies and to calculate the percentage of clinical trials that were registered in each country’s registry, and try to find and evaluate the factors determining that percentage. Design and Methods: The present study is a cross-sectional study using data from clinical trials registered from January 1, 2011, to December 31, 2015. Only countries with more than 2000 registered trials were included for further study. Ten countries met that criterion: United States, Japan, Iran, Australia, New Zealand, China, India, Germany, United Kingdom, and Netherland. The percentage of clinical trials that were registered in each country’s registry was calculated, and the factors determining that percentage were sought and analyzed through an exploratory approach. Results: The chi-squared test of independence indicated that the rate of clinical trial registration significantly differed between countries. From the adjusted standardized residuals, the percentage of clinical trials that were registered in the country of origin was higher in the United States, India, Japan, and Australia/New Zealand than in the European Union and China. Conclusion: The United States requires that informed consent documents for clinical trials contain clinical trial registration numbers from ClinicalTrials.gov, which could be the reason for the extremely high percentage of registered clinical trials (94%). Since the European Union does not have this requirement, clinical trials conducted in the European Union do not have to be registered in the countries in which they are conducted.
文摘The effectiveness of medical interventions should be based on the results of all properly conducted clinical trials, whether or not the trials have been published. The results of unpublished trials are systematically different from those that are published; they tend to be "negative" (find no effect or harm) or fail to support the interests of the funding agency. Therefore, relying on published trials alone can provide a biased view of effectiveness and safety. Registration of clinical trials at their inception, in widely available registries, makes it possible for all stakehold-
