| Purpose of researchWe collected the placebo-controlled clinical research projects of traditional Chinese medicine(TCM),which were published on CNKI in the last 10 years.We analyzed and evaluated the target disease,the course of the trial,the type of control and the adverse event in the clinical study of traditional Chinese medicine.In combination with the ethical requirements of the clinical trials of the drug,we discussed the general situation,indications,the characteristics and rules of adverse events in the placebo-controlled clinical study of Chinese medicine as well as the application principles of placebo in clinical research of TCM.It provides a reference for the clinical researchers of TCM to carry out research and conduct ethical review.It can also improve the quality of clinical research and ethical review and protect the safety and interests of the majority of the subjects at the same time.MethodsThe first part:Summarized and analyzed the existing laws and regulations on the use of placebo at home and abroad.The second part:In CNKI,we used the subjects below:a placebo&clinical trial(or clinical study)&Chinese medicine(or Chinese Medicine)to find the placebo-controlled study of traditional Chinese medicine,which was published from January 1,2007 to January 1,2016.All trials and clinical reports of placebo controlled clinical trials of Chinese medicine were included.We collected the basic information,indications,control methods,the course,adverse events and so on.Then put the data in the statistical research program and analyze statistically.Excel 2010 is used to collate the information into the database and introduce the IBM SPSS 21 software for data mining,and use the method of descriptive statistics to analyze the frequency and proportion of the overall characteristics of the data.The third part:Based on the example of TCM clinical placebo usage specification.Research results1 The first part1.1 It is ethical to use placebo control without effective intervention.1.2 The use of placebo is ethically acceptable in terms of "convincing or scientifically based methodological reasons" and "no serious or irreversible injury" with recognized and effective intervention.1.3 In drug clinical trials,we can use placebo-controlled cases for ethical conflicts.2 The second part2.1.1 The general situation of the placebo-controlled clinical trials of traditional Chinese medicine.A total of 1767 clinical research projects of traditional Chinese medicine(TCM)from January 1,2007 to January 1,2016 were collected.Reading headlines and abstracts,we included 1043 items of clinical trials that met the standard.The placebo-controlled trial involved 25 clinical departments.2.1.2 The distribution of placebo control in each year.According to the time of completion of each clinical trial,we analyzed the distribution of clinical trials of Chinese medicine with placebo as control.In 2015,the proportion of the placebo-controlled clinical trials of Chinese medicine was the highest,the percent was 15%.In 2007,the percent was opposite,5.4%.From 2007 to 2015,the quantity of the clinical study of Chinese medicine with placebo control increased gradually.2.1.3 The distribution of indications in clinical research of traditional Chinese medicine with placebo as control.According to the different research departments of the clinical trials of Chinese medicine,we included the total number of items and the proportion of various specialties,analyzing the application of the placebo in different specialties.There were 24 clinical majors,the highest proportion was the Department of Cardiology,and the lowest proportion was ICU.The proportion from the highest to the lowest was 147 in Cardiology Department(14.09%)>132 in Neurology Department(12.66%)>99 in Endocrinology Department(9.49%)>97 in Respiratory Department(9.30%)>79(7.57%)in Obstetrics and Gynecology Department>55 in Oncology Department(5.27%)>54 in Digestive Department(5.17%)>48 in Orthopaedics(4.60%)>44 in liver disease(4.22%)>35 in Rheumatism Department(3.36%)=35 in Pediatrics(3.36%)>28 in Urology Department(2.69%)>26 in Nephrology Department(2.49%)>23 in Infectious Disease Department(2.21%)>19 in Dermatological Department(1.82%)>18 in Hematology Department(1.73%)=18 in Surgical Department(1.73%)>14 in Ophthalmology Department(1.34%)>13 in Anorectal(1.25%)= 13 in E.N.T.department(1.25%)=13 in Health care department(1.25%>11 in Geriatric department(1.05%)=11 in Stomatology Department.(1.05%)>7 in Neurosurgery(00.67%)>4 in ICU(00.38%)?2.1.4 Distribution of placebo in different types of diseasesThe 1043 clinical studies of placebo-controlled Chinese medicine were categorized according to the nature of target diseases.The proportion of placebo control for chronic disease targeted trials(89%)was higher than that of acute diseases(11%);the proportion of placebo control in organic diseases was(84%)higher than that of functional diseases(16%);the proportion of nonself-limited diseases with placebo control was(94%)higher than that of self-limited disease.The proportion of the placebo control was(6%).2.1.5 The type of controlIn 1043 placebo-controlled clinical studies of traditional Chinese medicine,only 83%of the placebo-controlled subjects were just placebo-controlled,and with a placebo control combined with a positive drug control less than 17%.1043 clinical studies which had basic treatment(53%),and no basic treatment accounts for 47%.2.1.6 The course of clinical trialWe included 1020 clinical trials of traditional Chinese medicine.With the increasing of the treatment course,the number of clinical trials of traditional Chinese medicine with placebo was reduced,from the highest to the lowest:0.5 month to 1 month(25.20%)>less than 0.5 month(22.15%)>1 month to 2 months(18.92%)>2 months to 3 months(18.43%)>3 months to 6 months(9.80%)>6 months to 12 months(3.73%)>12 months to 24 months(1.77%).2.1.7 The application of placebo in different therapeutic efficacyA total of 220 items were counted.The proportion of clinical items which selected the subjective index as the main therapeutic target was 25.9%far higher than that of the clinical items with positive drugs 13.2%.The ratio of the clinical items with the positive drugs was 31.4%higher than that of the placebo controlled clinical items when the objective index was the main therapeutic target,and the proportion of the clinical items was 29.5%.2.1.8 Adverse eventsA total of 135 adverse events were reported in detail,including 8221 cases.Adverse events occurred in 873 cases,891 times,in 135 research projects describing adverse events,the incidence of adverse events was 10.8%,affecting factors including the disease itself,the adverse reactions produced by the basic treatment,the adverse reactions produced by the placebo and other factors.There were only 50 of placebo treatment,3118 subjects in placebo group,Adverse events occurred in 175 cases,181 times,in 50 clinical trials with only placebo treatment,the incidence of adverse events was 5.8%,affecting factors including the self reaction of the disease,the adverse reactions produced by the placebo and other factors;In the 135 clinical trials,there were 85 items of adverse events with placebo and basic treatment,with a total of 5103 cases in the placebo group,698 cases of adverse events,710 times,in 85 clinical studies with basic treatment,the incidence of adverse events was 13.9%,the factors affecting the incidence were self reaction of the disease,adverse reactions produced by basic treatment,adverse reactions produced by placebo and its factors.2.2 Summary2.2.1 From 2007 to 2016,the clinical research project of placebo-controlled in Chinese medicine showed an increasing trend year by year.2.2.2 It is ethical to use placebo control in some functional and self limited diseases.2.2.3 When target disease has standard treatment and can not be interrupted,it is often considered to use placebo-controlled in basic treatment,that is,"superposition design".2.2.4 We should set up a reasonable course of treatment and visiting point according to the purpose of the study,the characteristics of the target disease and the pharmacodynamic data in the early stage of the drug.2.2.5 In the design of clinical plan of traditional Chinese medicine,placebo should be considered,in order to get a relatively objective test result,when the subjective index is used as the main therapeutic target.2.2.6 Attention should be paid to the research and the exploration of the placebo preparation,choosing the placebo rationally according to the research purpose,and pay attention to the adverse events of placebo.3 The third part3.1 In the design of clinical trials for rheumatic diseases,ethical requirements should also be taken into full consideration.If the placebo control is applied,the superposition design can be considered.3.2 According to the purpose of the experiment and the characteristics of the disease,we should set up the treatment course and the visiting point rationally.3.3 We should pay attention to reporting and tracing of adverse events,as well as completing contingency plans.Conclusions1 When we use placebo,we should give full consideration to ethical requirements.2 According to the purpose of the experiment and the characteristics of the target disease,through reasonable design,making the clinical trials of Chinese medicine meet the requirements of science and ethics,and improve the level of clinical research of traditional Chinese medicine through reasonable scheme design.3 We should pay attention to the research and exploration of placebo-preparation,rational selection of placebo based on research purpose,and focuse on the adverse events of placebo. |
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