Establishing an evaluation mode with multiple primary outcomes based on combination of diseases and symptoms in TCM clinical trials

Abstract

The development of a scientific evaluation tool is a prerequisite to reflect the efficacy of traditional Chinese medicine (TCM). At present, separate analysis of each outcome is the most commonly used method in randomized controlled trials (RCTs) of TCM, while this method has been reported to have some limitations. Combination evaluation of multiple primary outcomes including diseases and symptoms can reflect the efficacy of TCM comprehensively and objectively. Now, several multivariate statistical methods have been proposed to analyze RCTs with multiple clinical outcomes. In this article, we highlighted the two commonly used methods, global statistical test (GST) methodology and alphaadjustment procedures, and introduced an evaluation mode. First, we used one stage adaptive adjustment strategy to estimate the correlation among multiple primary outcomes in blindness, which can resolve the inappropriate correlation estimation among multiple primary outcomes, then we introduced an adaptation of the Bonferroni procedure which can account for correlated data to calculate the alpha of individual outcome.GST using O'Brien ranking procedure and the corresponding global treatment effect (GTE) measure were used to assess the treatment's global impact. We will conduct a randomized, double-blind, controlled trial with compound Danshen dripping pills for stable angina to explore establishing the evaluation mode. We hope that the introduction of this approach can provide methodological aid for the assessment of therapeutic effect of TCM.

The Use of Multiple Primary Outcomes in Randomized Controlled Trials of Chinese Herbal Medicine

“…Since the holism perspective of TCM, as well as the multidimensional of the reported outcomes (patient-reported, laboratory test, clinician-rated and TCM syndrome outcomes, etc. ), it is not practical to identify a single most important outcome as the primary outcome to summarize the effect of CHM [ 35 ]. Our previous study also had proposed an efficacy evaluation system with multiple primary outcomes, which is based on the holism benefit of TCM, integrated the primary outcome by three domains: western medicine-specific outcome, TCM syndrome outcome, and quality of life [ 12 ].…”

“…Therefore, reporting more than one primary outcome in CHM trials may be appropriate because a single measure may not sufficiently characterize the effect of a Chinese herbal formula on a broad set of domains [ 10 , 11 ]. Multidimensional primary outcomes, which can incorporate the laboratory test, traditional Chinese medicine- (TCM-) diagnosed information (e.g., tongue coat, pulse, face color, and mind), and clinician-concerned and patient-reported outcomes have been proposed [ 12 , 13 ]. When there is a lack of clear consensus on the most important clinical outcome, combined with the need to examine clinical effectiveness on related outcomes spanning disparate domains, encourage the use of multiple primary outcomes [ 14 ].…”

Study protocol for yoga-based lifestyle intervention for healthy ageing phenotype in the older adults (yHAP): a two-armed, waitlist randomised controlled trial with multiple primary outcomes

“…Since we aim to capture a holistic effect of YBI across the multiple domains of HAP, we propose to use the global statistical test (GST) to assess the efficacy of the intervention. 35 36 However, in view of non-availability of preliminary data, unknown nature of correlations among the outcome variables and their distribution, we prefer to choose a sample size of n1−n2=100, which is in line with the adequate sample size proposed for 10 multiple outcomes (K), under the simulations reported for sample size calculations with computation of the global treatment effect under various possible settings by Huang et al 35 Further, since the reported efficiency of GST to summarise a treatment's merit is not compromised with small sample sizes, we could avoid the risk of being underpowered. 37 Further, keeping in view of the attrition rate of 25% over 6 months, we derived a sample size of n=250 for the present study.…”

Systems Pharmacology for Investigation of the Mechanisms of Action of Traditional Chinese Medicine in Drug Discovery

“…Therefore, how to predict the drug combination of these TCM and WM and assess the efficacy and side effects is valuable for novel drug design. At present, RCTs have been generally used to assess the clinical efficacy of TCM (Hu et al, 2017). For example, a meta-analysis of RCTs has shown that TCM significantly improved analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and total effectiveness rates of knee osteoarthritis.…”

“…Therefore, the optimization of the ADME properties of lead compounds may be a critical factor that determines whether the drug can be successfully developed (MacCoss and Baillie, 2004). Many clinical studies including randomized controlled trials (RCTs) of the herbs have been conducted, some demonstrating hepatotoxicity and toxicity (Hu et al, 2017). However, because the extraction and isolation of compounds derived from herbs are costly and time-consuming, as well as only a few of them have satisfactory ADME properties and less side effects, there is an urgent need to develop a fast and effective novel strategy for identifying potential active compounds.…”