Designing and implementing multicenter clinical randomized controlled trials on moxibustion with large samples

Implementing clinical trials with large multicenter samples is an important way to scientifically evaluate and demonstrate the curative effect of moxibustion.At present,clinical trials on moxibustion with large multicenter samples are prospering in China.It is necessary for research units to have good research professionals and technical platforms as well as a highly standardized and scientifically feasible methodology of research.Taking tasks in the ongoing national 973 project and in the sci-tech support program of the "11th 5-year plan",for example,this research captures the characteristics of moxibustion,carries out deep analysis and introduces specific methods and the important significance of clinical research tasks on moxibustion in designing multicenter plans,implementing experiments,supervising quality and strengthening compliance.

Pivotal Factors Concerned in Design of Acupuncture Clinical Research:From Two Articles in JAMA

Two randomized controlled trials of acupuncture concerning polycystic ovary syndrome（PCOS） and stress urinary incontinence（SUI） were published simultaneously in the 24 th issue, 2017 of The Journal of the American Medical Association（JAMA）. A trial involving PCOS indicated that active acupuncture did not increase live birth compared with sham acupuncture; meanwhile, another trial referring to SUI showed that electroacupuncture resulted in less urine leakage compared with sham electroacupuncture. With an eye to the negative and positive results of acupuncture, three pivotal factors should be contemplated：（1） proper illness for acupuncture, that is, a problem need to be solved in current medical science, and acupuncture may really work for it;（2） proper pre-studied primary outcome, which is better be objective and repeatedly measurable to reveal the therapeutic effect of acupuncture truly and objectively;（3） proper sham control, which can blind the patients to the upmost extent with minimal biological effects. Through the publication of clinical trials of acupuncture in high-impact journals in recent years, researchers should have confidence in their clinical trials by pondering over these three pivotal factors.

Trial design of arch bridge of composite box section with steel web-concrete flange

The concrete arch bridge is a natural and appropriate structural solution,aesthetically pleasing and easily integrated into the environment,especially in mountainous and island areas.However,construction difficulty and cost will increase with heavy self-weight when the span enlarges.A potential solution is to use a composite box arch ring with steel web-concrete flange.Taking Wanzhou Yangtze River Bridge(the longest concrete arch bridge in the world with a main span of 420 m)as a prototype,trial designs of a composite box arch with steel webs(including corrugated steel webs and plain steel webs)and concrete flanges were carried out.Comparison of quantities and structural behaviors of the prototype concrete arch with the two trial designed composite arch was presented.It is shown that the selfweight of the composite arch can reduce about 28%and the structures can meet the design requirements,therefore it is possible to use the two composite arches in long span arch bridges.

Clinical efficacy observation of thalamic pain treated with acupuncture under the guidance of evidence-based medicine

Objective To study the feasibility of the crossover trial design and the minimal imbalance index random distribution method in the clinical small-sample-size randomized controlled trial（RCT） research of thalamic pain treated with acupuncture under the guidance of evidence-based medicine（EBM）.Methods The crossover trial design was adopted.Eleven cases with the definite diagnosis were randomized into a program-I group（6 cases,treated with acupuncture before western medicine） and a program-II group（5 cases,treated with western medicine before acupuncture） according to the minimal imbalance index method.In the statistical analysis,the groups were named as an acupuncture group and a western medicine group separately,11 cases in each one.Acupuncture was applied to Xìmén（郄门 PC 4）,Yīnxì（阴郄 HT 6）,Xuèhǎi（血海 SP 10）,etc.In the control treatment,Carbamazepine was prescribed for oral administration.Either the duration of treatment or the wash-out period was 10 days.The visual analogue scale（VAS） was adopted for the efficacy assessment.Results The total effective was 100.0%（11/11） after treatment in either group.The remarkably effective rates were 63.6%（7/11） and 36.4%（4/11） in the acupuncture group and the western medicine group separately,without statistically significant difference in comparison.Conclusion The crossover trial design and the minimal imbalance index distribution method can accomplish RCT of the clinical acupuncture and moxibustion research with the small sample size involved.They can provide the high-quality evidences for clinical acupuncture research.Acupuncture therapy can achieve the same therapeutic effect as Carbamazepine,the common western medicine,and the efficacy of it is potentially superior to that of western medicine.

Delayed treatment effect predicting(DTEP)model for guiding immuno-oncology trial designs

Background:The presence of delayed treatment effects(DTE)is common in immuno-oncology trials.However,conventional trial designs often overlook the potential presence of DTE,which can result in an underestimation of the required sample size and loss of statistical power.Conversely,when there is actually no apparent delay in treatment effects,alternative trial designs for addressing DTE may lead to an over-estimation of sample size and unnecessary prolongation of the trial duration.To mitigate this challenge,we propose the use of a DTE predicting(DTEP)model to better guide immuno-oncology trial designs.Methods:The DTEP model was developed and validated using data from 147 pub-lished randomized immuno-oncology trials.The eligible trials were divided into a training set(approximately 75%of the trials)and a test set(approximately 25%).We employed linear discriminant analysis(LDA)to develop the DTEP model for pre-dicting the DTE status using baseline characteristics available at the trial design stage.The receiver operating characteristic(ROC)curve was utilized to assess the ability of the model to distinguish between trials with and without DTE.We further re-conducted the JUPITER-02 trial in a simulation setting,employing three design approaches to assess the potential benefits of utilizing the DTEP model.Results:Baseline characteristics available during the trial design stage,including cancer type,line of treatment,and experimental and control arm regimens were incorporated,and high accuracy in predicting the DTE status in both the training set(area under the operating characteristic curve(AUC),0.79;95%confidence interval(CI),0.71-0.88)and test set(AUC,0.78;95%CI,0.66-0.90)was achieved.Notably,the model successfully predicted the DTE status in two randomized trials among the test sets that were conducted by our team(ESCORT-1st(absence of DTE)and JUPITER-02(presence of DTE)).In silico re-conduct of the JUPITER-02 trial further showed that the statistical power would be markedly improved when trial designs were guided by the DTEP model.Conclusions:The DTEP model can significantly enhance the precision and effectiveness of immuno-oncology trial designs,thereby facilitating the discovery of effective im-munotherapeutics in a more streamlined and expedited manner.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction(CODE-AAMI):Protocol for a Randomized Placebo-Controlled Trial

Background:Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction(AAMI)is an important factor in occurrence of heart failure which additionally results in poor prognosis.Therefore,the treatment of ventricular remodeling needs to be further optimized.Compound Danshen Dripping Pills(CDDP),a traditional Chinese medicine,exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.Objective:This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.Methods:This study is a multi-center,randomized,doubleblind,placebo-controlled,parallel-group clinical trial.The total of 268 patients with AAMI after primary percutaneous coronary intervention(pPCI)will be randomly assigned 1:1 to the CDDP group(n=134)and control group(n=134)with a follow-up of 48 weeks.Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction(STEMI),with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI,and the control group treated with a placebo simultaneously.The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI).The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide(NT-proBNP)level,arrhythmias,and cardiovascular events(death,cardiac arrest,or cardiopulmonary resuscitation,rehospitalization due to heart failure or angina pectoris,deterioration of cardiac function,and stroke).Investigators and patients are both blinded to the allocated treatment.Discussion:This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI.Patients in the CDDP group will be compared with those in the control group.If certified to be effective,CDDP treatment in AAMI will probably be advised on a larger scale.(Trial registration No.NCT05000411)