Research On The Development Of Reporting Guideline For Systematic Review Of Animal Experiments In The Field Of Traditional Chinese Medicine

Background: Systematic review of animal experiments has been considered as an effective way to improve the guiding value of animal experiments for clinical research and to reduce the risk of its results being transferred to clinical practice.In recent years,the number of published systematic review of animal experiments has gradually increased,but unfortunately,more and more studies show that the quality is low,and the phenomenon of inadequate and incomplete reports is still relatively common.The reporting guideline of medical research is one of the important ways to improve the quality of medical research.In 2006,Peters et al.proposed the reporting standard for systematic review of animal experiments,but they did not take into account the different types of animal experiments and characteristics of traditional Chinese medicine research,and which development was not based on scientific methods.So far,Peters’ s guideline is not indexed by the EQUATOR Network and not recognized by relevant international agencies.Objectives: Our study will adopt scientific methods to develop the reporting guideline for systematic review of animal experiments in the field of traditional Chinese medicine,to promote the transparency of the whole process of systematic reviews’ report,improve the quality of reports,and ultimately promote the transformation and utilization of preclinical evidence into clinical evidence.Methods:1)Systematic review: Firstly,we searched the Medline（via Pub Med）,Ovid-Embase,BIOSIS Previews,CNKI,CBM,Wan Fang Data,VIP database Data from establishment to December 31,2020 comprehensively.Then,evaluate the reporting quality and epidemiology characteristics of published systematic reviews of interventional animal experiments based on the PRISMA 2009 guideline,to understand and clarify the reporting status quo and existing problems,and to put forward suggestions,laying a foundation for determining the initial items of systematic review reporting guideline of traditional Chinese medicine animal experiments.2)Delphi method: We selected multidisciplinary experts across the country,and distributed enquiry tables by E-mail.Experts did not communicate with each other,and the importance of each item was rated back-to-back according to Likert 5-level scoring method,and open questions were set to collect expert opinions.Two rounds of Delphi survey were conducted in total.After each round,data were imported into Excel 2019 to conduct statistical analysis on the positive coefficient of experts（questionnaire recovery rate）,concentration degree of experts’ opinions（X）and coordination degree of experts’ opinions（CV）.Letter inquiry items X≥0.8* Full mark average score（5points）,i.e.X≥4 and CV≤0.25 can be included.3)Face-to-face expert consensus: National Institutes of Health（NIH）consensus forming conference method was adopted,and experts were selected through network inquiry and expert recommendation.Relevant materials will be sent to the invited experts before the meeting,during which the experts will discuss the list item by item and put forward suggestions for modification,and the experts will vote to decide whether to include or exclude the items.Consensus is reached when more than 75% of experts agree.After the meeting,experts reviewed and perfected the PRISMA-ATCM.4)Literature review analysis: Data from CNKI,CBM,Pub Med and Web of Science databases from January 2019 to December 2021 were searched systematically.The report quality of systematic review of animal experiments in the field of traditional Chinese medicine based on PRISMA-ATCM,and the research status was analyzed,for one thing,to understand the possible problems existing,for another to explore the applicability of PRISMA-ATCM in the evaluation of research in this field.Results:1)813 systematic reviews of animal experiments were included,which were published in 503 journals covering 52 countries and regions,and the number of published papers was increasing year by year.Neurological diseases were the most studied area（23.5%,191/813）,and rats were the most frequently included animals（70.8%,576/813）.An analysis of the quality of published systematic reviews of animal experiments based on the PRISMA 2009 guidelines showed that only 30.1%（245studies）were of good quality（> 21 points）with a mean of 18.9 ± 3.7 on a score of 9-27.An exploratory analysis of the related factors affecting report quality showed that the reports with more than 3 authors,those published after 2014 and those registered in advance all had higher report quality,and the difference was statistically significant compared with the control group（P < 0.05）.2)35 experts accepted the invitation and completed two rounds of Delphi expert letter consultation from February 2021 to August 2021.Their research fields covered traditional Chinese medicine,clinical medicine,basic medicine,methodology,statistics and medical journal editing.The questionnaire recovery rate was 100%.We received61 open expert opinions.In the first round,the mean importance score of all items was≥4.0 and CV < 0.25（except item 8," Protocol and Registration ",CV = 0.27,for the second letter consultation）,so all items were included.In the second round,12 items（4a,6b,6c,8b.1,9a,9b,9c,9d,10 d.1,11 a,11b,12）with significance score ≥4.0 and CV < 0.25 were deleted.6 items with importance score < 4.0（1a,8b.2,8c.1,8c.2,10 a.1,10 b.1）were excluded.For items with importance score ≥4.0 and CV > 0.25,the research group discussed and decided to exclude（1b,10 a.2,altogether）and adjust（8f,1）some items.Finally,10 items and 26 sub-items were determined to be included in the list of items in the consensus meeting.3)Eight experts held an online face-to-face expert consensus meeting on October 17,2021.Twelve items were revised and expanded against the PRISMA 2009 checklist,namely Item 1（Title）,Item 2（Structured summary）,Item 3（Rationale）,item 4（Objectives）,Item 5（Protocol and registration）,6（Eligibility criteria）,Item 11（Data items）,14（Planned methods of analysis）,Item 18（Study characteristics）,Item 24（Summary of evidence）,Item 25（Limitations）,Item 27（Funding）.Finally,PRISMAATCM,a 27-item systematic review reporting guideline for animal experiments in the field of Traditional Chinese medicine,was developed.4)A total of 52 systematic reviews of traditional Chinese medicine animal experiments were included,including 12 in Chinese and 40 in English,covering 11 countries and regions,published in 34 different journals respectively.The number of studies in which the first author was from China was the largest（34/52,65.4%）,and 42（80.8%）were in the experimental group using Chinese（herbal）drugs alone.Thirtyseven studies（71.2%）included only in vivo experiments in animals,and all studies used rats and/or mice,with the largest range of diseases being neurological diseases.PRISMA-ATCM guideline was used to evaluate the reporting quality of included studies.The scores were 10.9-26.8 points,with an average of 20.08 ± 4.68,and only26.92%（14 reports）had good quality（> 24 points,high transparency）.Essential items were inadequate in terms of purpose（description of dose-effect conversion）,registration,inclusion of information on standard outcome measures,data items（information report on animal models and control interventions）,study characteristics（information report on control interventions）,and discussion of limitations.Conclusion:1)At present,the overall reporting quality of published systematic reviews of animal experiment is low,transparency is not high,especially for the animals and characteristics of traditional Chinese medicine information report is not sufficient.Terefore,it is necessary to research and development of traditional Chinese medicine field of animal experiment system review report guide,improve the quality of reports in this field,in the end the transformation of pre-clinical evidence to clinical.2)The preparation process of PRISMA-ATCM guideline conforms to the existing international guidelines,and makes up for the deficiency of PRISMA 2009 guideline that are not applicable to animals and Chinese medicine interventions.The development of PRISMA-ATCM guideline will help to improve the reporting transparency of systematic review of animal experiment in the field of traditional Chinese medicine.3)Based on PRISMA-ATCM guideline,the quality of published reports on systematic review of animal experiments in the field of traditional Chinese medicine is not high,especially the reports on traditional Chinese medicine and animal characteristics are not enough.It is necessary to take measures to accelerate the promotion and use of PRISMA-ATCM guideline in the future.In order to standardize the writing of scientific research papers on systematic review of animal experiments of traditional Chinese medicine,and ultimately improve the overall quality of systematic reviews in the field of animal experiments.4)PRISMA-ATCM guideline are the first consensus-based reporting guidelines for systematic review of animal experiments in traditional Chinese medicine.The release of PRISMA-ATCM guideline will promote the reporting quality of systematic review of animal experiments in traditional Chinese medicine,and improve the transparency of the whole process of systematic review of animal experiments in research design,implementation and reporting.In the future,it is necessary to take various measures to promote the improvement,popularization and application of PRISMA-ATCM guideline.