The reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of traditional Chinese medicine compound formulations and the differences between Chinese and non-Chinese trials.

BACKGROUND: An increasing number of randomized placebo-controlled trials involving traditional Chinese medicine (TCM) compound formulations have been implemented worldwide. OBJECTIVE: The aim of this study was to assess the reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of TCM compound formulations and compare these differences between Chinese and non-Chinese trials. METHODS: English-language databases included the following: PubMed, OVID, EMBASE, and Science Citation Index Expanded. Chinese-language databases included the following: Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific and Technological Periodical Database, and the China National Knowledge Infrastructure. All were searched from respective inception to March 2009 to identify randomized placebo-controlled trials involving TCM compound prescriptions. Two reviewers independently assessed the retrieved trials via a modified Consolidated Standard of Reporting Trials (CONSORT) checklist and some evaluation indices that embodied the TCM characteristics or the scientific rigor and ethics of placebo-controlled trials. Trial publishing time was divided into 3 intervals: phase 1 (≤1999); phase 2 (2000-2004); and phase 3 (2005-2009). The number and percentage of trials reporting each item and the corresponding differences between Chinese (mainland China, Hong Kong, and Taiwan) and non-Chinese (eg, Japan, United States, Australia, Korea, and United Kingdom) trials were calculated. Moreover, the influence of trial publishing time on the reporting of CONSORT items and the differences in the number of items reported for each time interval between Chinese and non-Chinese trials were assessed. RESULTS: A total of 324 trials from China and 51 trials from other countries were included. A mean of 39.7% of the CONSORT items across all Chinese trials and 50.2% of the items across all non-Chinese trials were reported. The number of the reported CONSORT items all increased over time in both groups and the gap between Chinese articles and non-Chinese articles gradually decreased. Additionally, of the 324 Chinese articles, 137 (42.28%) reported TCM syndrome type, 113 (34.88%) reported the diagnostic criteria of diseases for TCM, and 69 (21.30%) reported efficacy evaluation indices of TCM. Of the non-Chinese articles, 3 (5.88%) reported TCM syndrome type and 1 (1.96%) reported the diagnostic criteria of diseases and evaluation indices of efficacy for TCM. It was found that 45.37% and 6.17% of Chinese articles reported the standard intervention for the diseases being treated and the emergency plan, respectively, compared with 23.53% and 9.80% for the non-Chinese articles; 33.02% and 10.49% of Chinese articles reported informed consent and ethics committee approval, respectively, compared with 92.16% and 82.35% for the non-Chinese articles. With regard to placebo ethics, 38.89% of the Chinese trials and 23.53% of the non-Chinese trials found it would not be ethically acceptable to use placebo alone in the control group. CONCLUSIONS: The data indicate that the reporting quality of the included trials on TCM compounds has improved over time, but still remains poor regardless of Chinese or non-Chinese trials. Across all trials, particularly Chinese trials, the reporting of the CONSORT items was inadequate (39.7%). The difference in the mean number of the reported CONSORT items between Chinese trials and non-Chinese trials narrowed from phase 1 (10.0 vs 13.8) to phase 3 (14.4 vs 17.4). Moreover, a large number of trials, especially non-Chinese trials (94.1%), were lacking syndrome differentiation of TCM. More importantly, in many placebo-controlled trials, especially Chinese trials, the use of placebo was not justified and was ethically contradictory.

[Tanreqing Injection for community-acquired pneumonia: a systematic review of randomized evidence].

OBJECTIVE: To evaluate the efficacy and safety of Tanreqing Injection, a compound traditional Chinese herbal medicine, for community-acquired pneumonia. METHODS: Literatures about randomized controlled trials of Tanreqing Injection for community-acquired pneumonia were reviewed. Related literatures were selected and analyzed according to different treatment strategies of the trials. The methodological quality of the trials was assessed by the Jadad scale, and evaluation was performed. RESULTS: Twelve randomized controlled trials meeting the inclusion criteria were selected and reviewed. As Tanreqing combined group (Tanreqing Injection plus antibiotics and basic therapy) was compared with antibiotics group (antibiotics plus basic therapy), the meta-analysis indicated that the relative risk (RR) for the total cure rate was 1.51, and 95% confidence interval (CI) was [1.29, 1.77]; RR for the total obvious effect rate was 1.31,ls and 95% CI was [1.20,1.43]; RR for the effective rate was 1.17, and 95% CI was [1.11, 1.23]. The weighted mean difference (WMD) in disappearance time of fever between the two groups was -1.24, and 95% CI was [-1.71, -0.76]. The RR values between the two groups for the total obvious effect rate of cough and expectoration were 1.42 and 1.27, and 95% CIs were [1.16, 1.74] and [1.04, 1.55] respectively. The RR values between the two groups in absorption of chest X-ray shadow and neutrophil number were 1.19, 1.10 and 95% CIs were [1.09, 1.30], [1.03, 1.17] respectively. The differences were all statistically significant. Serious systematic adverse reactions had not been reported in the trials. CONCLUSION: The effect of combined therapy with Tanreqing Injection plus antibiotics and basic therapy is better than that of antibiotics plus basic therapy. Tanreqing Injection can improve the symptoms of cough and expectoration, shorten the fever time and facilitate the absorption of chest X-ray shadow, without any significant adverse reactions. However, further high-quality trials are needed.

[Chinese medicine for acute upper respiratory tract infection: a systematic review of randomized controlled trials].

OBJECTIVE: To evaluate the efficacy and safety of new drugs of traditional Chinese medicine (TCM) for acute upper respiratory tract infection (common cold). METHODS: Reports regarding randomized controlled trials of Chinese medicine for common cold were reviewed. Related reports were selected and the methodological quality of the trials was assessed by the Jadad scale. Meanwhile, the stratified analysis was made according to different TCM syndrome types of common cold. RESULTS: Thirteen randomized controlled trials consistent with the inclusion criteria were selected and reviewed. As TCM treatment group was compared with control group, the meta analysis indicated that the relative risk (RR) for obviously effective rate was 1.10, and the 95% confidence interval (CI) was [1.05, 1.16]; the weighted mean difference (WMD) of the onset time of lowering body temperature was -1.70, and the 95% CI was [-2.76, -0.65]. There were significant differences in the above evaluation indexes between the two groups (P=0.000 2, P=0.002). The WMD of disappearing time of fever was -1.32, and the 95% CI was [-3.14, 0.49], while there was no significant difference between the two groups (P=0.15). As the common cold patients with wind-heat syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.11, the 95% CI was [1.05, 1.19], and there was significant difference between the two groups (P=0.000 7). As the common cold patients with wind-cold syndrome in the TCM treatment group were compared with those in the control group, the meta analysis indicated that the RR for obviously effective rate was 1.07, the 95% CI was [0.99, 1.16], and there was no significant difference between the two groups (P=0.10). Serious adverse reactions had not been reported in the trials. CONCLUSION: TCM new drugs developed in recent years for preventing and treating common cold have better therapeutic effects than the old ones. They can accelerate the onset time of lowering body temperature and improve the symptoms of common cold without any significant adverse reactions. Because of lacking of placebo-controlled and blank-controlled studies, further high-quality trials are still needed.

Baicalin Inhibits Lipopolysaccharide-Induced Inflammation Through Signaling NF-κB Pathway in HBE16 Airway Epithelial Cells.

Baicalin, a flavonoid monomer derived from Scutellaria baicalensis called Huangqin in mandarin, is the main active ingredient contributing to S. baicalensis' efficacy. It is known in China that baicalin has potential therapeutic effects on inflammatory diseases. However, its anti-inflammatory mechanism has still not been fully interpreted. We aim to investigate the anti-inflammatory effect of baicalin on lipopolysaccharide (LPS)-induced inflammation in HBE16 airway epithelial cells and also to explore the underlying signaling mechanisms. The anti-inflammatory action of baicalin was evaluated in human airway epithelial cells HBE16 treated with LPS. Airway epithelial cells HBE16 were pretreated with a range of concentrations of baicalin for 30 min and then stimulated with 10 µg/ml LPS. The secretions of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) in cell culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of IL-6, IL-8, and TNF-α were tested by quantitative real-time polymerase chain reaction (real-time RT-PCR). Furthermore, Western blotting was used to determine whether the signaling pathway NF-κB was involved in the anti-inflammatory action of baicalin. The inflammatory cell model was successfully built with 10 µg/ml LPS for 24 h in our in vitro experiments. Both the secretions and the mRNA expressions of IL-6, IL-8, and TNF-α were significantly inhibited by baicalin. Moreover, the expression levels of phospho-IKKα/ß and phospho-NF-κB p65 were downregulated, and the phospho-IκB-α level was upregulated by baicalin. These findings suggest that the anti-inflammatory properties of baicalin may be resulted from the inhibition of IL-6, IL-8, and TNF-α expression via preventing signaling NF-κB pathway in HBE16 airway epithelial cells. In addition, this study provides evidence to understand the therapeutic effects of baicalin on inflammatory diseases in clinical practice.