Current situation of Investigator-Initiated Clinical Trial quality management: A scoping review / 中华医学科研管理杂志

Objective:To systematically identify and summarizes the weaknesses of the key aspects of Investigator-Initiated Clinical Trial (IIT) quality management in China, and quantitatively assess these weaknesses with a synthesis of relevant evidence, thereby providing references for the subsequent establishment of a complete IIT quality management system in China.Methods:According to the Scoping review report checklist (PRISMA-ScR statement), we conducted a systematic literature retrieval and screening, data extraction, and result synthesis of IIT quality management issues after defining the research questions.Results:73 eligible studies were eventually included. It was found that the most frequently explored issues were a lack of guidance and support from methodological and statistical experts at the project initiation stage (60.9%), a lack of research funding or improper funding management at the project implementation stage (49.3%), mismanagement of archival materials at the project completion stage (70.0%). Meta-analysis results showed that after evidence synthesis, the incidence of irregular informed consent signing, untraceable raw data, delayed study progress, and protocol violation were all above 40%, but there was heterogeneity in the results.Conclusion:Some outstanding issues in IIT quality management need to be addressed. Future studies should conduct more practical research to obtain quantitative data, undertake demonstrative application of management protocols, further carry out pioneering exploration and research in the field of IIT quality management, and propose effective solutions and strategies to improve IIT quality.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Suggestions on reforming and improving the prevention and treatment system for major epidemic diseases in China / 中华流行病学杂志

Based on systematic review of the role of clinical treatment, disease control and scientific research, and combining with the problems exposed by the COVID-19 epidemic, suggestions were proposed to reform and improve the prevention and treatment system for major epidemics diseases in China. In clinical treatment, it is necessary to enhance clinical staff's awareness of law-based reporting, capabilities of syndromic surveillance, the use of infectious diseases reporting systems, and to improve national or local monitoring platforms for emerging infectious diseases detection. In terms of disease control, it is important to provide authorities to disease control departments through laws and regulations, improve the quantity and quality of related human resources, and strengthen the applied research and technical readiness targeted infections disease prevention, control and emergency preparedness. As for scientific research in major epidemic response, it is essential to strengthen research projects guided by national requests, build research institutions that can 'make a final decision', establish national and regional key laboratories, and strengthen strategic technical reserve for emergency disease control and treatment.

Introduction to PRISMA-CI extension statement and checklist systematic reviews on complex interventions / 中华流行病学杂志

Comprehensive interventions have been widely used in health system, public health, education and communities and have become increasingly focus of systematic reviews. There have been many reporting guidelines about systematic reviews, but they do not take the features of comprehensive interventions in medical area into consideration. As a result, PRISMA-CI has been developed as an extension of PRISMA, which adds or modifies the essential items of PRISMA. This paper introduces the items of PRISMA-CI and explains the items with an example to help authors, publishers, and readers understand PRISMA-CI and use it in systematic reviews on comprehensive interventions. As it become more and more popular with comprehensive interventions, PRISMA-CI will provide important structure and guidance for its systematic review and Meta-analysis.

Randomized controlled trial based on big data / 中华流行病学杂志

A large amount of data has been accumulated in Chinese medical area. Problems as how to use big data to carry out randomized controlled trials have also been increasingly noteworthy. Through learning the successful experiences in conducting randomized controlled trials on big data from abroad, this article introduces the knowledge regarding sources of data, identification of research subjects and outcomes, interventions, methods of randomization and the implementation of informed consent, etc., all related to big data, hoping to shed light on studies of this kind, for the years to come in China.

An overview of validation methods based on the medical claims database / 中华流行病学杂志

Medical claims database is an important source of data for studying the characteristics, and burden of diseases, to provide a basis for the development of policy on management. The database is usually used to identify patients through International Classification of Diseases and free text-building algorithms, thus it is crucial to validate whether the algorithm is correctly identifing the targeted population. This paper introduces both traditional and emerging validation methods including machine learning, natural language processing and database linkage etc.. We also have tried to present a suitable validation method for the current situation in China, so as to promote the application of big data in medical areas and to provide reference for epidemiology studies, based on medical claims database in this country.

Developing process of guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019) / 中华流行病学杂志

Pharmacoepidemiology refers to the use of epidemiological research methods in studying the application and use of drugs in large populations to evaluate the safety and efficacy of medical products. Therefore, standardized pharmacoepidemiology research is the basis of the above work. Based on systematic reviews of national and international pharmacoepidemiological methodological standards and guidelines, and in combination with Chinese medical and health practice and experts’ opinions, the Professional Committee of Pharmacoepidemiology of Chinese Pharmaceutical Association developed the group standard, guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019), to better guide the work of pharmacoepidemiology. The guideline was designed to provide advice and reference for pharmacoepidemiology research by government, regulatory agencies, research institutions, and pharmaceutical manufacturers in China.

Scoping review of active surveillance systems for vaccine safety world-wide / 中华预防医学杂志

Objective@#To identify post-marketing active surveillance systems for vaccine safety around the world and understand their features and mechanisms, in order to provide guidance for vaccine administration activities in China.@*Methods@#Following the steps of scoping review, literature about active surveillance system for vaccine safety and published by 30 June 2018 were identified by searching electronic databases, including PubMed, Scopus, and Cochrane Library. Grey literature were also sought by exploring relevant websites. Identified literature were screened according to eligibility criteria, and informative data from included literature were then charted. Framework Synthesis and Thematic Analysis were performed to integrate the charted data.@*Results@#97 pieces of literature were included for review, and 11 active surveillance systems for vaccine safety were identified, mostly located in developed countries. These systems were constructed by 3 types of organizations: administration departments, academic or research institutions, and health care providers. Their data sources included immunization registries, electronic medical records, claims data, case reports of adverse events following immunization electronic questionnaires, and epidemiologic study data. According to their operation procedures, these systems were grouped into 4 modes of active surveillance: Data Linkage, Investigator Network, Automatic Follow-up System, Studies Consortium.@*Conclusion@#Practice of active surveillance for vaccine safety greatly varies across countries, with different conditions and advantages. It is suggested that developing countries should choose suitable mode of active surveillance considering their local situations.

Develop the active surveillance system for vaccine safety in China / 中华预防医学杂志

Post-marketing surveillance of vaccine safety is an important measure to detect adverse events following immunization and therefore reduce the harms to public health. The conventional method for safety surveillance is a passive way through spontaneous reporting, which suffer from under-reporting and incomplete. While active surveillance, a newly proposed surveillance method in developed countries, is capable to make up the deficiencies of passive surveillance. The surveillance system of vaccine safety in China is currently using passive surveillance, and facing many problems and challenges. This arouses a need to promote development of an active surveillance system for vaccine safety in China, learning from the experience world-wide. This commentary aims to throw out suggestions for establishing the active surveillance system, according to the specific situation in China and based on a scoping review of literature.

Introduction on 'assessing the risk of bias of individual studies' in systematic review of healthcare intervention programs revised by the Agency for Healthcare Research and Quality / 中华流行病学杂志

This paper summarizes the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions revised by the Agency for Healthcare Research and Quality (AHRQ) and introduces how to use Revman software make risk of bias graph or risk of bias summary.AHRQ tool can be used to evaluate following study designs:RCTs,cohort study,case-control study (including nested case-control),case series study and cross-sectional study.The tool evaluates the risk of bias of individual studies from selection bias,performance bias,attrition bias,detection bias and reporting bias.Each of the bias domains contains different items,and each item is available for the assessment of one or more study designs.It is worth noting that the appropriate items should be selected for evaluation different study designs instead of using all items to directly assess the risk of bias.AHRQ tool can be used to evaluate risk of bias individual studies when systematic reviews of health care interventions is including different study designs.Moreover,the tool items are relatively easy to understand and the assessment process is not complicated.AHRQ recommends the use of high,medium and low risk classification methods to assess the overall risk of bias of individual studies.However,AHRQ gives no recommendations on how to determine the overall bias grade.It is expected that future research will give corresponding recommendations.

Introduction on 'assessing the risk of bias of individual studies' in systematic review of healthcare intervention programs revised by the Agency for Healthcare Research and Quality / 中华流行病学杂志

This paper summarizes the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions revised by the Agency for Healthcare Research and Quality (AHRQ) and introduces how to use Revman software make risk of bias graph or risk of bias summary.AHRQ tool can be used to evaluate following study designs:RCTs,cohort study,case-control study (including nested case-control),case series study and cross-sectional study.The tool evaluates the risk of bias of individual studies from selection bias,performance bias,attrition bias,detection bias and reporting bias.Each of the bias domains contains different items,and each item is available for the assessment of one or more study designs.It is worth noting that the appropriate items should be selected for evaluation different study designs instead of using all items to directly assess the risk of bias.AHRQ tool can be used to evaluate risk of bias individual studies when systematic reviews of health care interventions is including different study designs.Moreover,the tool items are relatively easy to understand and the assessment process is not complicated.AHRQ recommends the use of high,medium and low risk classification methods to assess the overall risk of bias of individual studies.However,AHRQ gives no recommendations on how to determine the overall bias grade.It is expected that future research will give corresponding recommendations.

Screening study of 2017 Chinese rare disease survey list based on expert consensus / 中华医学科研管理杂志

Objective To preliminary formulated 2017 Chinese rare disease survey list by experts consensus.Methods By using checklist methods,we selected studied diseases from five available rare disease data sources in China.By summarizing,proofreading,removing of duplicate data,the primary survey list with 344 diseases was formulated.By organizing two rounds of consensus conferences,experts voted and revised the survey list,then ultimately formulated 2017 Chinese rare disease survey list.Results According to the poll,in selected 344 rare diseases which were discussed in consensus conferences,54 diseases were suggested to be deleted,9 pairs of diseases were suggested to be incorporated.For Chinese and English names of these rare diseases,306/344 diseases conform to nomenclature by discussion.According to the experts' tips and advice,we revised the primary survey list and ultimately formulated 2017 Chinese rare disease survey list including 281 diseases.Conclusions Experts consensus combines the scientificity of methodology and clinical experience of experts.In the background of medical big data and targeted poverty alleviation,the early stage of study is in accordance with the main stream of thought for the national survey of rate disease in China.

Efficacy of the traditional Chinese medicine NAOAN capsule for primary prevention of stroke in high-risk population / 中华健康管理学杂志

Objective To evaluate the efficacy of the traditional Chinese medicine NAOAN capsule in primary prevention of stroke in high?risk populations. Methods A multicenter, randomized controlled study was performed in community setting, involving 1 088 individuals at high risk of stroke, with cerebrovascular function scores<75 and 10?year Framingham stroke risk ≥6%. Subjects were recruited in communities at Beijing, Shanghai, Changsha, and Chengdu communities, through resident committees or the village unit. A total of 559 subjects were randomized into a group treated with the NAOAN capsule, and 529 subjects in an aspirin treatment group. Follow?up was performed every 2 months for 2 years. At the mid?point and end of the intervention, we compared cerebrovascular function differences between the 2 groups. Results During the 2?year community trial, 531 subjects in the NAOAN capsule group and 465 in the aspirin group followed the protocol. Cerebrovascular function scores increased from 45.2±19.7 at baseline to 61.7±26.5 after the 2?year trial (t=－12.931, P<0.001) in the NAOAN capsule group, and from 47.2±18.9 at baseline to 53.7 ± 25.1 (t=－5.058, P<0.001) in the aspirin group; greater increases in cerebrovascular function scores were found in the NAOAN capsule group than that in the aspirin group (t=4.906, P<0.001). Conclusions Cerebrovascular function in individuals at high risk of stroke was improved by taking NAOAN capsule. Cerebrovascular function scores improved more with NAOAN capsules than with aspirin.

Risk of bias assessment: (9) Application of the risk of bias assessment results / 中华流行病学杂志

In this last paper of the series about risk of bias assessment,we introduce the application of risk of bias assessment results.Risk of bias assessment is one of the key steps in the assessment of quality of evidence.The risk of bias assessment results could be the “diagnosis” of individual studies,which helps decision making related to the inclusion and exclusion of individual studies,as well as the data analysis in the systematic review process.This paper focuses on how to incorporate risk of bias assessment results in the GRADE assessment for quality of evidence,including the principles and the tips for the application.

Diagnostic accuracy of line probe assays for drug-resistant tuberculosis: a Meta-analysis / 中华流行病学杂志

Objective To evaluate the diagnostic accuracy of line probe assays for drugresistant tuberculosis (TB) in China.Methods Chinese databases (CNKI,Wanfang,SinoMed,VIP Information) and English databases (PubMed,Embase,Cochrane Library) were used to retrieve the literatures regarding the accuracy of line probe assays in the diagnosis of drug-resistant tuberculosis in China between January 1,2000 and September 1,2017.Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the included studies.Sensitivity and specificity in different studies (using drug sensitivity test or gene sequencing as gold standard) were combined by Meta-analysis using bivariate or univariate model.In addition,subgroup analysis (GenoType MTBDRplus,GenoType MTBDRsl and Reverse dot blot hybridization) and sensitivity analysis were also carried out.Results A total of 24 literatures involving 82 studies were included in the final analysis.The sensitivity and specificity of line probe assays for rifampicin resistant TB were 0.91 (0.88-0.94) and 0.98 (0.97-0.99),respectively.The sensitivity and specificity of line probe assays for isoniazid resistant TB were 0.80 (0.77-0.83) and 0.98 (0.96-0.99),respectively.The sensitivity and specificity of line probe assays for multidrug-resistant TB were 0.81 (0.76-0.85) and 0.99 (0.99-1.00),respectively.The sensitivity and specificity of line probe assays for quinolone resistant TB were 0.92 (0.88-0.95) and 0.94 (0.91-0.97),respectively.The sensitivity and specificity of line probe assays for second-line injectable drug resistant TB (including kanamycin,Capreomycin,amikacin) were 0.79 (0.58-0.91) and 0.98 (0.90-1.00),respectively.The sensitivity and specificity of line probe assays for extensively drug-resistant TB were 0.46 (0.19-0.75) and 1.00 (0.98-1.00),respectively.Subgroup analysis showed that the overall diagnostic accuracy of GenoType MTBDRplus and GenoType MTBDRsl was higher than that of Reverse dot blot hybridization.According to the results of sensitivity analysis,the results of this study were robust.Conclusion The diagnostic accuracy of line probe assays for drug-resistant TB is high.

Risk of bias assessment: (8) Risk of Bias in Systematic Review (ROBIS) / 中华流行病学杂志

This paper introduces the Risk of Bias in Systematic Review (ROBIS),including:1) the development of ROBIS,2) three phases of ROBIS tool judging the overall risk of bias that related to systematic reviews,and 3) illustration on the application of ROBIS in a published systematic review.ROBIS is the first rigorously developed tool which is specifically designed to assess the risk of bias in systematic reviews.ROBIS will help improve the process of risk assessmcnt on bias which appeared in overviews and guidelines.

Risk of bias assessment: (7) Assessing Bias in Studies of Prognostic Factors / 中华流行病学杂志

This paper introduces the tools related to Quality In Prognosis Studies (QUIPS) to assess the risk of bias in studies of prognostic factors and the relevant points of assessment and to illustrate the application of QUIPS in published prognostic research.The QUIPS tool identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors including participation,attrition,measurement on prognostic factors,outcomes,confounding factors,statistical analysis and reporting.It also provided a new method for evaluation on bias in the areas of prognostic research.

Antibiotic use in emergency departments of class Ⅲ general hospitals in China / 中华流行病学杂志

Objective To investigate the utilization of antibiotics in emergency departments (EDs) of class Ⅲ general hospitals in China.Methods Data from a national monitoring network for rational use of drugs was used.The data included prescriptions of EDs from 114 class Ⅲ general hospitals in 30 provinces (autonomous regions,municipalities) of China.A total of 10 260 595 prescriptions from October 1,2014 to December 31,2016 were extracted.The Anatomical Therapeutic Chemical Classification/Defined Daily Dose (DDD) system was used for the classification of antibiotics and calculation of antibiotic use intensity.An auto-regression model was used to analyze the trend over time and seasonal variation of antibiotic use in EDs.Results The rate of antibiotic prescriptions was 27.82％ in EDs,among the antibiotics prescribed,25.58％ were for the combination therapy with 2 or more antibiotic agents,and injectable antibiotic prescriptions accounted for 60.59％.Besides,the number of DDDs per 100 patient visits was 81.84.Broad-spectrum agents were the most commonly used antibiotics,among which the second and third generation cephalosporins,quinolones and macrolides accounted for 23.83％,21.68％,19.17％ and 7.89％ of all prescribed antibiotics,respectively.The use of antibiotics,including prescription frequency and use intensity,in EDs had a slight but significant increase tendency (P＜0.05),and the seasonal variation of antibiotic use in EDs was obvious,characterized by the highest frequency and intensity of antibiotic use in winter,the differences were significant (P＜0.05).Conclusion The antibiotic prescription rate in EDs of class Ⅲ general hospitals in China was controlled at a low level,but the proportions of broad-spectrum antibiotics and injectable antibiotics were high,and a significant increase trend in antibiotic use in EDs was found.

Spatial-temporal analysis on pulmonary tuberculosis in Beijing during 2005-2015 / 中华流行病学杂志

Objective To analyze the spatial distribution and identify the high risk areas of pulmonary tuberculosis at the township level in Beijing during 2005-2015.Methods Data on pulmonary tuberculosis cases was collected from the tuberculosis information management system.Global autocorrelation analysis,local indicators of spatial association and Kulldorff's Scan Statistics were applied to map the spatial distribution and detect the space-time clusters of the pulmonary tuberculosis cases during 2005-2015.Results Spatial analysis on the incidence of pulmonary tuberculosis at the township level demonstrated that the spatial autocorrelation was positive during the study period.The values of Moran's I ranged from 0.224 3 to 0.291 8 with all the P values less than 0.05.Hotspots were primarily distributed in 8 towns/streets as follows:Junzhuang,Wangping,Yongding and Tanzhesi in Mentougou district,Yancun in Fangshan district,Wangzuo town in Fengtai district,Tianqiao street in Xicheng district and Tianzhu town in Shunyi district.Spatiotemporal clusters across the entire study period were identified by using Kulldorff's spatiotemporal scan statistic.The primary cluster was located in Chaoyang and Shunyi districts,including 17 towns/streets,as follows:Cuigezhuang,Maizidian,Dongfeng,Taiyanggong,Zuojiazhuang,Hepingjie,Xiaoguan,Xiangheyuan,Dongba,Jiangtai,Wangjing,Jinzhan,Jiuxianqiao,Laiguangying,Sunhe towns/streets in Chaoyang district,Houshayu and Tianzhu town in Shunyi district,during January to December 2005.Conclusion Incidence rates of pulmonary tuberculosis displayed spatial and temporal clusterings at the township level in Beijing during 2005-2015,with high risk areas relatively concentrated in the central and southern parts of Beijing.

Risk on bias assessment: (6) A Revised Tool for the Quality Assessment on Diagnostic Accuracy Studies(QUADAS-2) / 中华流行病学杂志

This paper introduced the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2),including the development and comparison with the original QUADAS,and illustrated the application of QUADAS-2 in a published paper related to the study on diagnostic accuracy which was included in systematic review and Meta-analysis.QUADAS-2 presented considerable improvement over the original tool.Confused items that included in QUADAS had disappeared and the quality assessment of the original study replaced by the rating of risk on bias and applicability.This was implemented through the description on the four main domains with minimal overlapping and answering the signal questions in each domain.The risk of bias and applicability with'high','low'or'unclear'was in line with the risk of bias assessment of intervention studies in Cochrane,so to replace the total score of quality assessment in QUADAS.Meanwhile,QUADAS-2 was also applicable to assess the diagnostic accuracy studies in which follow-up without prognosis was involved in golden standard.It was useful to assess the overall methodological quality of the study despite more time consuming than the original QUADAS.However,QUADAS-2 needs to be modified to apply in comparative studies on diagnostic accuracy and we hope the users would follow the updates and give their feedbacks on line.