Systematic Evaluation Of Placebo In Clinical Trials Of Traditional Chinese Medicine

Purpose： Included in recent10years compared to placebo for large sample, multi-centerclinical trial of new drug of TCM project, through to the target in placebo-controlled clinicaltrials of traditional Chinese medicine (TCM) disease, placebo the occurrence of adversereactions, and the placebo effect analysis and evaluation, and so on and so forth, to explorefor placebo controlled clinical trials of traditional Chinese medicines of indications, andcharacteristics of the placebo effect and adverse reactions. In order to provide materials andplacebo for new drug clinical trial application data.Material and method：Consulting in January2004-December2013,10years by thestate food and drug administration shall be presided over by56drug clinical trial institutionaccredited by the new drug of traditional Chinese medicines and participate in clinical trials,included all to placebo controlled clinical trial of new drug of TCM project plan and summaryreport/statistics report, indications, adverse reactions of placebo and to placebo research of theplacebo effect. Project basic information in the first part of the test solution, indications, drugsand treatment effective data statistical analysis, discusses the application of traditionalChinese medicine clinical trials in the placebo disease characteristics, etc.; In the second partof the project summary/statistics report adverse reactions were statistically analyzed, thecharacteristics and principles of placebo adverse reactions; The third part of the projectsummary/statistical report analyzed the placebo effect, comprehensive analysis of the placeboeffect in different diseases, and the influence factors of the placebo effect.Results：1. The first part of research results1.1included with placebo controlled clinical trials of traditional Chinese medicines generalsituation of the project.Included a total of553Chinese medicine clinical trial projects, with a placebo controlled trial project235, accounting for42.50%of the total project, placebo-controlled clinical trialproject involves17professional69diseases;1.2regarding to placebo controlled clinical trial of new drug of TCM project distribution ofeach year.The proportion of each year to a placebo controlled trial project distribution, project thehighest percentage of83.33%in2013,2004,2005, the lowest0.00%. After2008, comparedto placebo as a dramatic increase in the experimental study, and showed a trend of increasingyear by year;1.3compared to placebo for the distribution of Chinese traditional medicine new drug clinicaltrial project indications.1.3.1placebo in different clinical studies, anorectal highest (100%), onset the lowest (25%).Top five and high to low in turn is: the anus bowel division (100%)> digestive department16(64.00%),>oncology5(62.5%)> rheumatism11(61.11%)> pediatric21(60%).1.3.2placebo in the application of different kinds of diseases, compared to placebo for69kinds of disease, including11kinds of diseases such as functional constipation, functionaldyspepsia, gouty arthritis and so on are all made of placebo-controlled.1.3.3placebo in the application of different nature of the disease, aiming at functional diseasedisease of project selection, placebo-controlled clinical trials (64.52%) than the proportion oforganic disease project proportion (39.71%); The selection of acute placebo-controlled rate(41.32%) and chronic diseases (42.82%) is close to; Self-limited disease chooseplacebo-controlled proportion (53.91%) than a self-limited disease proportion (39.06%) of theproject.1.3.4placebo effect in different evaluation index test, the application of subjective indicatorsas the main curative effect evaluation of projects, the placebo (61.08%) than the proportion ofthe objective index of proportion (33.15%) of the project.1.3.5in the pilot program of235compared with placebo, placebo-controlled projectsaccounted for only88.51%, the "three arm experiment design"(10.64%); In pure adoptsplacebo-controlled.2.The second part of the results of the study2.1placebo adverse reactions included basic situation of the project 85items included placebo-controlled clinical trials, the placebo group of8561cases, a total of50cases of adr,53, a placebo adverse reaction rate were0.58%,0.62%respectively.rheumatism placebo adverse reaction rate as high as1.06%, followed by geriatrics department(0.98%)> orthopedic (0.89%), anorectal incidence of adverse reactions to a minimum of0.00%.2.2placebo adverse reactions involving systems, organs and clinical manifestationAdverse reactions involving multiple systems, the proportion of each system from high to lowin turn as follows: the digestive system0.32%>skin and accessories0.23%> nervous system0.02%>cardiovascular system0.04%>endocrine system0.04%.2.3placebo diagnosis, degree of adverse reactions, measures and resultsAdverse reactions to diagnosis, symptoms and signs diagnostic83.02%> experimentalabnormal16.98%> disease diagnosis16.98%; Degree of adverse reactions, mild94.34%>moderately3.77%> severe1.89%; Adverse reactions to determine the causal relationship,may/suspicious90.57%>sure related5.66%> likely to be3.77%; Adverse reaction steps,continue to use92.45%> completely stop using5.66%> reduce dose1.89%> interrupt use0.00%; Adverse reaction results, lost52.83%> relieve41.51%and> unknown3.77%;Adverse reactions are not out of the clinical trial94.39%> exit test experiment5.66%.2.4placebo dose relationship with adverse reactionsDose50g or less when the highest incidence of adverse reactions, was1.30%, the second,1500g <dose1600g when the incidence of adverse reactions was1.14%, or less dose during1100-1200incidence of adverse reactions to a minimum of0%.2.5volume increase and the relationship of adverse reactionsOnly drug test was used to simulate agent when the incidence of adverse reactions was0.56%,drug test simulation combined positive medicine simulation doses when the incidence ofadverse reactions was0.71%.2.6course relationship with adverse reactionsShort course of treatment up to0.64%incidence of adverse reactions, followed by shortcourse of treatment by0.60%, the lowest incidence of0.23%for a long period of treatment.2.7dosage forms and the relationship of adverse reactions Only use simulated experiment medicine agent, patch the highest incidence of adversereactions, at2.06%, followed by tablets0.73%, gel, suppositories, oral liquid, paste, thelowest incidence of adverse reactions, is0%. Experimental medicine agent mergepositive-controlled simulation agent, when using topical patch+capsule up to1.46%incidence of adverse reactions, followed by particle+capsule1.39%, pill+tablet, pill+capsulehas the lowest incidence of adverse reactions, is0%3. The third part of the results of the study3.1the placebo effect, included basic situation of the projectProject for72placebo-controlled projects,6942cases, involving13major,34species ofdisease.3.2placebo in each system diseases had certain placebo effect, different diseases with theplacebo effect. According to the main curative effect index of the disease, the placebo effectas high as61.25%in the common cold,followed by functional dyspepsia56.8%. The placeboeffect in the disease of abnormal glucose tolerance effect, lowest of0.76%. There were43projects placebo effect at20%-50%, accounts for60.65%of the total projects.3.3when the duration of less than or equal to14days, the placebo effect is highest, at43.18%,when the duration is more than3months less than or equal to6months, with the minimum ofthe placebo effect, is only6.05%.3.4the placebo effect when using frequency4times a day as high as52.92%,1times a daywhen the lowest33.39%. The placebo effect from high to low in turn is: every4times(52.92%)>2times a day (40.08%)>3times a day (35.36%)>6times a day (35.2%)>1times a day (33.39%).Conclusion：1. in clinical trials with functional disease or self-limited disease as the test drug target,recommend the use of placebo-controlled.2.whether to adopt placebo-controlled clinical trial with no obvious correlation of acute andchronic disease.3. in the design of clinical trial scheme, elected take subjective index as the main efficacy ofdisease index, recommend the use of placebo-controlled. 4. the placebo-controlled clinical trials, treatment shoulds not be too long, it is advisable to3months.5.should attach importance to the high incidence of adverse reactions of professional(rheumatism, geriatrics, orthopaedic), but also pay attention to and strengthen the research ofthe technics for placebo especially external preparation of Chinese medicine and explore.6.adverse reactions mainly affects the digestive system, skin and accessories, characterized bythe local administration of nausea, diarrhea, upset stomach, reaction (such as skin rashes,itching).7. incidence of adverse reactions with the dosage increase with the increase of the volume8.placebo incidence of adverse reactions has no obvious correlation with the dose within thecourse of treatment.9.placebo diagnosis of adverse drug reactions (adrs) are mainly composed of symptoms andsigns diagnosis, degree of adverse reactions are mild, adverse reactions measures to continueto use the majority of adverse reaction results in the majority.10.the placebo effect in clinical background is widespread, different disease the placebo effectis not the same.11. placebo effect on subjective strong illnesses such as pain as the primary symptom ofdisease have higher effect, a high proportion of natural rehabilitation of diseases, the placeboeffect is also high.12. the strength of the placebo effect, duration and research have a certain correlation studyfor more than3months, the strength of the placebo effect will decrease, the placebo effectand use frequency has no obvious correlation.