Constructing A Core Indicator Set For Safety Evaluation Of Clinical Research On The Treatment Of Bradyarrhythmias With Integrated Traditional Chinese And Western Medicin

Background:Arrhythmia is a common cardiovascular disease in clinic,among which the incidence of bradyarrhythmia shows an increasing trend year by year.Due to the influence of environment,pressure and other factors,its onset age is gradually getting younger.In modern medicine,Western medicine and cardiac pacemaker implantation are often used to treat bradyarrhythmia.In recent years,with the continuous development of traditional Chinese medicine(TCM),a large number of clinical studies have emerged on the treatment of bradyarrhythmia using the diagnosis and treatment model of integrated traditional Chinese and Western medicine.The results show that the clinical effect is better than that of TCM or Western medicine alone.However,the safety evaluation of integrated traditional Chinese and Western medicine in the treatment of bradyarrhythmia is relatively complex,and whether the addition of TCM has the effect of "enhancing effect and reducing toxicity" remains to be studied.In similar clinical trials,there are problems such as non-standard research design,report content,low level of evidence,etc.,and the methodological process of the core outcome set of clinical research safety evaluation that can reflect the characteristics of TCM has not been established systematically.Therefore,it is necessary to carry out research to unify the safety evaluation outcomes of clinical studies on bradyarrhythmia,and construct a core set of safety evaluation outcomes suitable for clinical studies on the treatment of bradyarrhythmia by integrated traditional Chinese and western medicine.Objective:The core outcome set for safety evaluation in clinical research on the treatment of bradyarrhythmia by integrated traditional Chinese and western medicine is constructed to reduce potential selective reporting bias by standardizing the clinical safety evaluation outcomes that must be reported.Meanwhile,multiple clinical research results can be integrated,which is conducive to the comparison and combination of systematic review/meta-analysis,in order to provide support for the safety evaluation of clinical research on the treatment of bradyarrhythmia by integrated traditional Chinese and western medicine.Methods:The methods of this study will consist of four stages:①We will develop a preliminary list of candidate adverse reactions/events related to the treatment of bradyarrhythmia with integrated traditional Chinese and western through drug package instruction review,systematic review and patients’ semi-structured interview.②Make a Delphi questionnaire according to the preliminary list,and obtain the judgment of different expert groups on the importance of outcomes through the two rounds of Delphi survey.③Patients’ views will be obtained through a questionnaire survey to supplement candidate outcomes and form a preliminary outcome set for safety evaluation.④A consensus meeting will be held to vote and discuss the outcome set of safety evaluation initially formed,and finally a core outcome set of safety evaluation suitable for clinical studies of integrated traditional Chinese and western medicine in the treatment of bradyarrhythmia will be formed.Results:85 articles meeting the criteria were included,including 56 in Chinese and 29 in English,and 6 drugs’ package instruction were reviewed.A total of 144 safety evaluation outcomes were extracted from them.After standardization and merging,70 safety evaluation outcomes were included in the original list of adverse reactions/events in clinical research on the treatment of bradyarrhythmia by integrated traditional Chinese and western medicine.There were five outcomes on which all experts reached consensus in the Delphi round 1 and eight outcomes on which all experts reached consensus in the Delphi round 2.There were 13 outcomes for which there was no consensus after patient questionnaire survey.After two rounds of Delphi survey and one round of patient questionnaire survey,35 outcomes were retained for the consensus meeting.In the consensus meeting,17 experts from four different stakeholder groups were invited to vote and discuss the candidate outcomes.After that,the consensus outcomes were graded according to the American Standard for General Terminology of Adverse Events.Finally,the core outcome set for safety evaluation in clinical research on the treatment of bradyarrhythmia by integrated traditional Chinese and western medicine was formed,including 14 outcomes of safety evaluation.The core outcome set is divided into doctors’reporting outcomes(including allergic reactions,arrhythmias,cardiac arrest,hypotension,death,hemorrhage(excluding central nervous system),and acute myocardial infarction)and patients’ reporting outcomes(including palpitation,chest distress,dizziness,syncope,fatigue,sweating,and dysphoria).At the same time,a self-reported core adverse reactions/events questionnaire is developed for the treatment of bradyarrhythmia by integrated traditional Chinese and Western medicine.Conclusion:This study formed the core outcome set for the safety evaluation of clinical research on the treatment of bradyarrhythmia by integrated traditional Chinese and Western medicine.It includes physician/patient reporting outcomes,patient self-reported core adverse reaction/event questionnaire and corresponding recognized evaluation tools.It conforms to international standards and takes into account the characteristics of TCM.The core outcome set has a guiding role in improving the clinical research design and evidence transformation of bradyarrhythmia in TCM.Due to the lack of recognized standards for safety evaluation of TCM,it is necessary to strengthen the development and research of characteristic outcomes of TCM.In the future,the application of the core outcome set of safety evaluation in clinical research should be promoted to help improve the grade of evidence in TCM clinical research.