Study On The Standardized Design Elements And Quality Evaluation Methods Of Case Report Forms For Clinical Trials Of Traditional Chinese Medicin

BackgroundThe design of the research protocol is the cornerstone of a clinical trial.If it is to be implemented into the recruitment of clinical subjects,all elements related to the research must be condensed and summarized into another document,the case report form(CRF).CRF,as the most commonly used tool for collecting clinical trial data,is the most intuitive embodiment of the research program,and acts as a bridge between trial design and implementation.The"Clinical Data Quality Management Practice" issued by the American Clinical Data Association clearly states that CRF is the most important document in clinical trials except for the research protocol,and its quality directly affects the quality of research data.Therefore,we must attach great importance to the standardized design of CRF.In recent years,tens of thousands of clinical trials have been carried out to evaluate the effectiveness and safety of traditional Chinese medicine,but few are of high quality.The guiding principles or specifications for quality control of clinical trials of traditional Chinese medicine.As for the design of CRF,there is always a lack of standardized,quality-controllable,and practical methodological guidance in line with the characteristics of traditional Chinese medicine.To this end,it is necessary to comprehensively sort out and analyze the data related to CRF design at home and abroad and in the field of traditional Chinese medicine(referred to as TCM-CRF)design difficulties and other issues,and carry out research on the standardized design methodology of TCM-CRF based on demand.Objective1.Systematically sort out the current situation and research progress of CRF design at home and abroad and in the field of traditional Chinese medicine,extract and summarize relevant laws and regulations,guiding principles,industry standards,and CRF design elements in books and documents;2.Through qualitative interviews and questionnaires,understand the method elements of TCM-CRF design by TCM clinical researchers and their cognition of design-related issues;3.On the basis of literature research,interviews and current situation investigation,formulate the TCM-CRF standardized design list and quality evaluation checklist to provide reference for the standardized design of TCM-CRF;4.Taking the previous TCM clinical research of our team as an example,to demonstrate the use of the TCM-CRF standardized design checklist and quality evaluation checklist,and to provide practical guidance for TCM-CRF designers.Methods1.Literature reviewSystematic review of domestic and foreign laws and regulations,guidance documents,and industry standards related to CRF design in clinical trials in the field of traditional Chinese medicine,and included books related to clinical trial CRF design by searching Pubmed,CNKI,Wanfang,VIP databases and university libraries.And literature,sort out the current situation,existing problems and difficulties of CRF design,and extract and summarize the relevant elements of CRF design in the above search data.2.Qualitative interviews and questionnairesThe qualitative interview part adopts the semi-structured individual interview method and the purposeful sampling method to conduct interviews with 13 TCM clinicians and scientific research workers from 4 tertiary hospitals,to understand the method elements of designing TCM-CRF and the design related issues.Cognitive situation,interview data using Nvivo12 qualitative data analysis software.The questionnaire survey adopted the method of convenience sampling to investigate the current situation and cognition of TCM-CRF design among 373 TCM clinicians and scientific researchers nationwide.The questionnaire data was analyzed by SPSS 26.0 software.3.TCM-CRF standardized design checklist constructionFor the universal items in the list,mainly from the CRF design element extraction results of the literature research part—CRF content extraction,including CD ASH,ICH-GCP,GCDMP,domestic GCP,and 12 CRF design related books and 13 literatures on CRF Description of the content;for the TCM-related items in the list,mainly from the interviews,questionnaires,and the extraction of TCM-related CRF design elements in the literature research section,and refer to the published TCM compound prescriptions,acupuncture,and single-case randomized controlled studies CONSORT clinical TCM-related items in the Trial Reporting Specification and Standard Items for Clinical Research Protocols of Traditional Chinese Medicine(SPIRITTCM).Based on the above content,expand the description of the individual data modules in the list.4.TCM-CRF quality evaluation checklist constructionThe universal items in the quality evaluation checklist are mainly from the extraction results of CRF design elements in the literature research part—the extraction of CRF design principles,including guidance documents such as ICH-GCP,GCDMP,and domestic GCP,as well as 12 books and 12 documents.,precautions,etc.,and refer to the structural elements such as the data module of the TCM-CRF standardized design list.For the TCM-related items in the quality evaluation checklist,it mainly comes from the CRF design principles and precautions related to TCM in the literature research section,as well as the TCM-CRF standardized design list for TCM-related items and extended explanations.5.List usage guide and demoTaking the three clinical studies of the previous research project of this research team "Evidence-based optimization and efficacy mechanism of traditional Chinese medicine prevention and treatment of coronary heart disease(angina pectoris-myocardial infarction-heart failure)" as examples,it shows how to use TCM-CRF to standardize the design list and the quality evaluation checklist to design a complete and quality controllable TCM-CRF.For the demonstration process construction,reference is made to the key elements of the CRF design process in the literature research and interviews and questionnaires section.Results1.In the literature review section,the international ICH-GCP and GCDMP,CDASH standards and domestic GCP,"Clinical Trial Data Management Work Guidelines","Drug Clinical Research Data Management and Statistical Analysis Plan Guidelines","Chinese Medicine New Drug Clinical General Principles of Research","Technical Guidelines for Clinical Research of New Chinese Medicines with Syndromes",and 14 books and 25 literatures,extract and summarize the key elements related to CRF design in the above materials,including CRF design principles,processes,content and Fill out the guide.2.The results of the qualitative interview and questionnaire survey include three aspects:(1)Problems:when TCM clinical researchers design TCM-CRF,the design time point is not reasonable,the design method is not standardized,and there are "more is better" in the data fields,etc.(2)Design elements:extract the key elements that researchers believe to design TCM-CRF from the results of interviews and questionnaires,including design process,design method and design points of TCM-related data;(3)TCM-CRF Design difficulties and requirements:The respondents believed that the design difficulties included that they could not find the normative guidance for the design of TCM-CRF,did not know how to judge the quality of the design,and did not know how to reflect the relevant elements of traditional Chinese medicine characteristics;the requirements included:in the design of TCM-CRF From time to time,there are norms to follow,to achieve controllable quality,and to show the characteristics of traditional Chinese medicine-related data.3.Construction of the TCM-CRF standardized design list:The list includes a total of 30 data modules,including one-time collection data modules such as demographics,past medical history,inclusion and exclusion information,etc.;multiple collection data modules such as vital signs,physique Inspections,laboratory tests,etc.;cumulative collection data modules such as concomitant medication,adverse events,etc.In addition,it includes necessary data modules such as homepage,headers and footers,and filling instructions,and provides data fields and field descriptions corresponding to each data module,for example,the fields corresponding to the demographic data module include gender,date of birth,and ethnicity.Among them,items related to traditional Chinese medicine data are added to the data modules of "disease conditions","intervention","drug distribution and recovery","questionnaire scale" and"combined medication" in the 30 data modules,such as the diagnosis of syndromes and the efficacy score.Table;"Intervention" module adds fixed composition of Chinese medicine compound,Chinese medicine injection,Chinese patent medicine and individualized Chinese medicine compound,acupuncture,massage/cupping/guasha/moxibustion and other related items;in the extended description part of the TCM-CRF standardized design list,provides detailed reference for the construction of data modules such as filling instructions and adverse events;and provides the dynamic changes of "diagnosis and treatment" and the design considerations of TCM-CRF under the five common research modes of traditional Chinese medicine,including the combination of disease and syndrome,and the combination of syndrome and disease.,the corresponding research model of prescriptions and syndromes,and the research model of single-case randomized controlled trials of traditional Chinese medicine and parallel medical records co-constructed by doctors and patients.4.Construction of TCM-CRF quality evaluation checklist:The checklist starts from 7 aspects of TCM-CRF design participants,design time point,overall design points,structural elements,problem statement and wording,layout and format,and characteristic elements of traditional Chinese medicine.The evaluation list was constructed,including a total of 90 items,and each item was evaluated in the manner of "yes,no,not applicable".For example,the main points of the overall design include "whether to collect data outside the study","whether there is duplication of data collection","ensure that the collected data is consistent with the requirements of the research protocol","ensure that the version and copyright of the CRF scoring tool are clear","ensure the collection of Original data rather than derived data" and other 9 items;in the layout and format section,including "ensure sufficient space for free text filling","minimize free text settings,and enable researchers to complete the form by the method of choice as much as possible",26 items including "font size,page margins,table borders and shading shall be consistent";the characteristic elements of traditional Chinese medicine include"ensure that syndrome diagnosis and efficacy evaluation tools have good reliability,validity and responsiveness" "If there is no suitable syndrome evaluation tool,it is necessary to ensure that the evaluation method complies with industry norms and has obtained expert consensus","there is a specific description of the scoring criteria when conducting syndrome evaluation",and "consolidated medication should be standardized and recorded when conducting new Chinese medicine research.At least 23 quality check items including reasons for medication,name of medication,dose,frequency,start and end date of medication" should be included.5.TCM-CRF Standardized Design Checklist and Quality evaluation checklist User Guide and Demonstration Section:Combined with literature research,interviews and current situation investigation,the key elements related to the design process of the case report form are extracted,a flow chart is formed,and two lists are marked The methods and steps used in the process will be demonstrated by taking the team’s three previous TCM clinical studies as examples.When TCM clinical researchers design a TCM-CRF for a study,the general process is:review the research plan→review the research flow chart→determine the data modules,fields and layout formats,question wording(with the help of TCM-CRF to standardize the design list and quality)Evaluation checklist)→complete the first draft design→review and revision(with the help of two checklists,comparative study protocols,multi-party expert review,pre-filling)→TCMCRF approval→TCM-CRF design completed→clinical use of TCM-CRF→during use Revisions and Version Changes(with two checklists for revisions).ConclusionThis research focuses on the actual problems existing in the design of TCM-CRF,conducts research,finds out the bottom line,systematically and completely sorts out the problems that need to be solved in this field,and extracts and summarizes domestic and foreign and Chinese The key elements of CRF design in clinical trials in the field of medicine,the TCM-CRF standardized design list and the TCM-CRF quality evaluation checklist are constructed,and the universal items and related items of traditional Chinese medicine are provided to provide reference for the design of TCM-CRF.The team’s previous TCM clinical research was used as an example to demonstrate the use and process of the checklist,which is of practical value to the majority of TCM clinicians and researchers.