A Study To Explore Establishing Specifications For Registration Of Traditional Chinese Medicine Clinical Trial

1. Objective1.1Analyze clinical register characteristics of TCM in American ClinicalTrials.gov.1.2Evaluating registered quality of TCM interventional studies to provide an objective basis for the formulation of TCM clinical trial registration specification.1.3Registration standard for clinical randomized and controlled trials of TCM will be preliminary formulated.2. Materials and Methods2.1Source of MaterialsTCM clinical trials from American register center of ClinicalTrials.gov.2.2Document RetrievalWe retrieved all the registered clinical trials from the building of ClinicalTrials.gov to the day of December20,2013with the term of "Chinese medicine" or "traditional Chinese medicine" by basic search retrieval form.2.3Inclusion and exclusion criteriaTCM clinical trials in this study were defined as interventions toward TCM research which included Chinese herbal compound, single herb, herbal extracts, herbal injections, Chinese patent medicine, acupuncture, cupping and qigong Organizers excluded TCM units such as sponsor or responsible units, or the location of implementation in TCM unit, but intervention was non-TCM research.2.4Data entry and processingExcel tables were adopted to entry all terms of trials included in this study. The terms covered20items including registration number, research status, organizers, time of first registration,time for study beginning, study purpose,research type, kinds of disease, interventions, control measures, medical intervention type, experimental stage, study design, random, blind method, muti-center study, research endpoint classification, total sample size, gender, host country/region, etc. All data was entered in English according to registry settings of United States ClinicalTrials.gov. All data were processed with SPSS18.0, and adopted EXCEL table to assist graphs.2.5Registered Quality EvaluationThis study assessed registration quality of TCM interventional research on clinical trials. In this study we adopted a kind of evaluation chart for interventional measures made by ourself and another kind of chart for intervention study methodology and twenty terms which met the minimum demand of WHO to assess quality of TCM2.6Making regestration standard for TCM clinical randomized and controlled trialsCombing with registered characteristics of TCM clinical trials in ClinicalTrials.gov and feature of TCM itself, we preliminary set up registered standard for TCM clinical randomized and controlled trials, relying on register content of international clinical trials and registered items’ setting of U.S. ClinicalTrials.gov and also referring to TCM Clinical randomized controlled trials report specification.3.Results3.1Total characteristics and times change of TCM clinical registration1China was the principal part of TCM clinical register, and USA following second.2TCM clinical trials were dominant by interventional study and mainly sponsored by colleges,universities and hospitals with evaluating the safety of drugs and/or effectiveness.3In interventional study, proportion of Chinese mainland host, corporation sponsor and multicenter study increased. On the contrary,corporation of Kong and Taiwanese sponsor, study being finished, status unclear study,Ⅲ phase clinical trial and published paper decreased.4Published clinical trials of TCM proportion was low and more registration information types missed and missing proportion was high.3.2Features of colleges, hospitals, scientific research institution and corporation sponsored trials1Colleges in Chinese mainland had higher proportion and mainly dominated by101-500sample size, single blind and medical intervention types belonging to others.2Hospital hosted trials in Hong Kong and Taiwan occupied more and USA was less.3Scientific research institutions or organizations sponsored trials in USA was more compared with other3types, also missing proportion of test staging information was highest.4There was more corporation sponsored trials in mainland, and medical intervention types belonging to medicine, Ⅳstage, sample size more than500and multicenter study occupied more.3.3Characteristics of Chinese mainland, Hong Kong and Taiwan and USA sponsored trials.1Chinese mainland had much higher proportion compared with Hong Kong,Taiwan and USA in test sample size of101-500, multicenter and Ⅳ stage clinical trials.2Chinese mainland, Hong Kong and Taiwan owned more ration in medicine, security or availability, parallel test, random and randomized trials.3Hong Kong and Taiwan had higher proportion in Ⅲ phase clinical trials and more published paper than Chinese mainland and the USA.4Hong Kong and Taiwan and USA carried out more trails of Ⅱ stage,sample size less than0-100and finished trails compared with Chinese mainland.5Proportion of American single group, open trial, effectiveness and endpoint classification information missing was higher than China, Hong Kong and Taiwan.6Stage information missing ratio of clinical trials in Chinese mainland and USA was higher than Hong Kong and Taiwan.3.4Registration quality of TCM clinical trialsFirstly,there was no trails with information completed in all162trails whose interventional type was TCM drugs. Secondly, description for interventional measures was incomplete with the highest score being7while lowest0and average being3.92Q1.76, which indicated TCM registration information on interventional measures lacked seriously.Thirdly,quality of methods for TCM registration was low with average score only being1.01±0.095.On the whole,TCM registration was in urgent need of normalization.3.5Preliminary finished making standard for TCM clinical randomized and controlled trialsWith referencing to register items of interventional research from the United States ClinicalTrials. Gov site,we modified9aspects including supplement TCM characteristics and content of the state,adding important part of clinical research plan,refine and remove part of original registration items, etc.,and preliminary developed35terms registration standard for TCM clinical randomized and controlled trials.4.Discussion4.1Pay more attention to intervention description to improve registration qualityIn order to improve report quality of TCM clinical trails,CONSORT work team authorized China to be responsible for formulating and publishing "CONSORT for TCM"."CONSORT for TCM" was on the basis of revised edition of CONSORT to supply contents which suited characteristic of TCM. And the interventional part especially emphasized that concrete content of all inventional measures from experimental group and control group should be described, such as drugs, dosage form, dosage, usage, treatment. This study on the basis of CONSORT for TCM assessed clinical trails quality whose interventional measures were TCM. The results show description for interventional measures was incomplete with the highest score being7while lowest0and average being3.92±1.76.And14.81%drug names were described widely, for example, TCM also be described with Chinese herbal Medicine and TCM treatment. In this study we also made a assessment table for TCM methodology description by ourselves based on the Jadad chart. And the table assessed production of random sequence, randomization concealment, randomization for implementation method, blinding, explanation for the basis of determining sample size and method of statistics. As a result, description of registration methodology was incomplete with average score only being1.01±0.095. We suggested on the one side clinical trial registration personnals should pay more attention to TCM interventions descriptions, on the other side, to refine the intervention terms of TCM and improve its clinical normalization and quality.4.2Improving integrity and standardization of registration informationOur study showed registration information of TCM clinical trials in ClinicalTrials.gov was incomplete and nonstandard. In all studies, information missing proportion of stage reached up to45.4%, and information missing ratio of terminal classification and purpose of research was respectively17.53%and11.78%. Other informations, like gender, sample size, blind method and test design were also discovered missing. There were various names for one prescription which can be seen from our study on formulations. For example, Tang, decoction and soup were one kind description for water-like formulations, also Wan and pill both for ball-like formulations. It also showed intervention measures were not united which included prescriptions’ initials shorted, or instead of Chinese spelling, code etc. These incomplete and nonstandard registration informations were neither beneficial for improving quality and transparency of TCM clinical trials, nor convenient for communication both at home and abroad. While registration system of peer review will avoid information missing or error effectively to provide guarantee for integrity of registration information.4.3Setting registration terms combined with TCM and national featureRegistration items of American ClinicalTrials.gov was based on modern medicine clinical trials and not combined with characters of TCM and other medicines. In other word, all these registers were designed for Western medicine clinical studies. However, such designs can’t accommodate TCM’s theoretical system which included diagnosis and treatments. For example, treatment principles, TCM syndrome types, types of intervention (acupuncture, decoction, parenteral administration of medicine, Chinese pre-formulated medicine combinations), and TCM specific outcome evaluation were all essential elements of TCM practice but can’t be included in the present format. And most importantly, as yet no standard nomenclature exists for the registration of TCM clinical studies. While all contents above is indispensable for TCM clinical trials. In addition, although TCM injections were applied generally and owned better effect, we also noticed much TCM injection information can’t be given such as its contained drugs, formula foundation, preparation method, adverse reactions and additives, which made people unclear about its basic informations. So it’s necessary to improve and refine registration items of ClinicalTrials.gov combined with TCM and national feature. Forming of registration items fitted for TCM clinical trials will made its registration more perfect and standard.4.4Standard finished preliminarily still need further improvementThis study preliminarily made a item listing for TCM clinical registration standard with reference to national related contents and combined with TCM trait,and provided guideline for TCM clinical registration. But the study was just prototype without basis of practice, which still need further improvement and modification by rounds of expert argumentation and soliciting opinions from all sides.