Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial

He, Jiayang; Li, Zhengtu; Huang, Wanyi; Guan, Wenda; Ma, Hongxia; Yang, Zi feng; Wang, Xinhua

drop out, payments will be pro-rated for the length of time they 387 stayed in the study, but payment will not be made until the study would have been completed. iii. Per-protocol population (PPP) 400 The PPP is all cases includes those cases that meet the inclusion criteria, are in full accordance 401 with the test program (or violate the protocol only slightly), complete the trial and complete the CRF. 402 The PP is used to analyse the main indicators for evaluating efficacy and to examine the consistency of 403 the results from the MITT. 404 iv. Safety analysis population (SAP) 405 After randomisation, the study drug is taken at least once and after intervention, effective safety 406 evaluation data has been recorded at least once. 407 In this experiment, the baseline data and efficacy analysis will be analysed by the MITTP. 408 Simultaneously, the primary efficacy endpoint will have PPP analysis, but the conclusions will be ii. All the statistical inferences will use two-sided tests. Statistically significant means P<0.05. The 417 confidence interval of the parameters will be estimated using a 95% confidence interval. 418 iii. Efficacy analyses of the LOCF will be used to compensate for the cases in which not all information 419 from the patients is recorded during treatment; the last observation data will transfer to the final test 420 results. The safety analysis will not estimate any missing data. minimum, maximum, P25, median and P75 will be provided; paired measurement data will also be 425 used to demonstrate the difference between the mean and standard deviation; and with non-parametric 426 methods, the median and mean rank will be provided. Count data are the frequency distribution and the 427 corresponding percentage. Level data will be given as the frequency distribution and the corresponding 428 percentage, as well as the median and mean rank. Qualitative information will show the positive rate, 429 the number of positive cases and the denominator. 430 vi. Baseline data analyses (two sets) will involve demographic indicators, the general situation and 431 primary and secondary indicators before the intervention. Measurement data will be analysed using the 432 t test or t² test (when the variance is not homogeneous); count data will be analysed using the Pearson's 433 χ 2 test. Rating data will be analysed using the two sample Wilcoxon rank sum test. x. For the safety analysis, the Pearson's χ 2 test will be used for comparing the prevalence of adverse 445 events (two sets) and the adverse events occurring in the trial will be listed and described. A description of the laboratory test results of normal/abnormal changes before and after the experiment, as well as the 447 relationship between abnormal changes and the test drugs will be recorded. These changes will also be 448 listed and described. The physician will decide whether to suspend observation of the patients. A follow-up survey will 456 carried out in the cases where the patient is withdrawn because of adverse events and the results will be 457 recorded in detail. At an appropriate time, the incidence of adverse events and treatments will be 458 reviewed and comprehensively analysed to determine whether the adverse events were related to the 459 study drug. 460 Adverse events leading to discontinuation of treatment or serious adverse events will be 461 summarised. In addition, the 95% confidence interval of adverse events using the Fisher's exact test 462 will be