Methodology guideline for clinical studies investigating traditional Chinese medicine and integrative medicine : executive summary

This guideline aims to provide a methodological guidance for clinical studies in TCM and integrative medicine in terms of study design, execution, and reporting. The commonly used methods including experimental and observational methods were introduced in this guideline such as randomized clinical trials, cohort study, case-control study, case series, and qualitative method which can be incorporated into above quantitative methods. The guideline can be used for the evaluation of therapeutic effect of TCM therapies or their combination with conventional therapy. TCM therapy refers to one of the followings or their combination: herbal medicine, acupuncture, moxibustion, cupping, Taichi/Qigong, and Guasha, Tuina (therapeutic massage). It is also suitable for research and development of ethnopharmaceuticals or folk medicine

Acupoint herbal patching for allergic rhinitis : a systematic review and meta-analysis of randomised controlled trials

Background: Acupoint herbal patching (AHP) is extensively used in treatment of allergic rhinitis in China. However, existing systematic review is insufficient. Objective of review: To evaluate the effectiveness and safety of AHP in treating allergic rhinitis. Search strategy: Wesearched seven electronic databases for randomised controlled trials (RCTs) from inception until August 2014. Evaluation method: Two authors selected studies, extracted data and evaluated risk of bias independently. The Cochrane risk of bias tool was applied to assess the methodological quality of the included trials, and REVMAN 5.2 software was utilised to perform data analysis. Results: Twenty RCTs involving 2438 participants were included. Most of them were evaluated as high risk of bias. Acupoint herbal patching significantly decreased the recurrence rate at 6 months compared with Western medicine (RR 0.52; 95% CI 0.42–0.64), and similar effect was found for AHP plus Western medicine versus Western medicine (RR 0.53; 95% CI 0.44–0.65). Acupoint herbal patching appeared to be more effective than placebo in improving total clinical symptoms and signs after treatment and at 6 months, and in improving quality of life at <3 months and over 3 months. No severe adverse effects were found in the AHP groups. Conclusions: Acupoint herbal patching alone or combined with Western medicine appears to be more effective than placebo or Western medicine, respectively. Acupoint herbal patching seems to be a safe treatment. However, the findings should be interpreted with caution. Further large-scale, rigorously designed trials are warranted to confirm the findings

Chinese herbal medicine as adjuvant treatment to chemotherapy for multidrug-resistant tuberculosis (MDR-TB) : a systematic review of randomised clinical trials

Introduction: Chinese herbal medicine (CHM) has been increasingly used as an adjuvant treatment for multi-drug resistant tuberculosis (MDR-TB) in China. To inform clinical practice, we performed a systematic review on the beneficial effect and safety of CHM for MDR-TB. Methods: We searched six electronic databases for randomised clinical trials (RCTs) of CHM for MDR-TB. We used RevMan 5.2 software for data analyses with effect estimates as risk ratio (RR) with 95% confidence interval (CI). Results: 30 RCTs involving 3374 participants with MDR-TB were included. The methodological quality was generally poor in terms of risk of bias. Meta-analyses favoured CHM plus chemotherapy on sputum bacteriological conversion rate compared with chemotherapy alone after initiation of treatment (6th mos: RR 1.27, 95% CI 1.14 to 1.41, n = 12; 12th mos: RR 1.30, 95% CI 1.11 to 1.52, n = 6; 18th mos: RR 1.19, 95% CI 1.11 to 1.27, n = 9). Compared with chemotherapy alone, meta-analyses showed benefit from CHM plus chemotherapy on lung lesions resorption rate (6th mos: RR 1.10, 95% CI 0.91 to 1.32, n = 5; 12th mos: RR 1.26, 95% CI 1.10 to 1.45, n = 4; 18th mos: RR 1.19, 95% CI 1.08 to 1.32, n = 7) and cavity closure rate (12th mos: RR 1.48, 95% CI 1.06 to 2.07, n = 2; 18th mos: RR 1.26, 95% CI 1.04 to 1.53, n = 5), relapse rate (RR 0.28, 95% CI 0.16 to 0.50, n = 4), and abnormal liver function (RR 0.56, 95% CI 0.46 to 0.69, n = 14). No serious adverse effects were reported. Conclusions: CHM as an adjuvant to anti-TB chemotherapy may have beneficial effect for MDR-TB in terms of bacteriological and radiological outcomes, and is relatively safe. However, due to poor methodological reporting of the included trials, a confirmative conclusion needs to be supported by further robust clinical trials

Oral Chinese proprietary medicine for angina pectoris : an overview of systematic reviews/meta-analyses

Background: Oral Chinese proprietary medicine (CPM) is commonly used to treat angina pectoris, and many relevant systematic reviews/meta-analyses are available. However, these reviews have not been systematically summarized and evaluated. We conducted an overview of these reviews, and explored their methodological and reporting quality to inform both practice and further research. Methods: We included systematic reviews/meta-analyses on oral CPM in treating angina until March 2013 by searching PubMed, Embase, the Cochrane Library and four Chinese databases. We extracted data according to a pre-designed form, and assessed the methodological and reporting characteristics of the reviews in terms of AMSTAR and PRISMA respectively. Most of the data analyses were descriptive. Results: 36 systematic reviews/meta-analyses involving over 82,105 participants with angina reviewing 13 kinds of oral CPM were included. The main outcomes assessed in the reviews were surrogate outcomes (34/36, 94.4%), adverse events (31/36, 86.1%), and symptoms (30/36, 83.3%). Six reviews (6/36, 16.7%) drew definitely positive conclusions, while the others suggested potential benefits in the symptoms, electrocardiogram, and adverse events. The overall methodological and reporting quality of the reviews was limited, with many serious flaws such as the lack of review protocol and incomprehensive literature searches. Conclusions: Though many systematic reviews/meta-analyses on oral CPM for angina suggested potential benefits or definitely positive effects, stakeholders should interpret the findings of these reviews with caution, considering the overall limited methodological and reporting quality. We recommend further studies should be appropriately conducted and systematic reviews reported according to PRISMA standard

Empirical evidence for outcome reporting bias in randomized clinical trials of acupuncture : comparison of registered records and subsequent publications

Background: Outcome reporting bias has received widespread recognition and been considered to pose two threats to the validity of clinical decision making because they overestimate the effect of treatments or distort the results of trials. However, the problem of outcome-reporting bias has not been systematically studied among randomized clinical trials of acupuncture. Our objectives were to evaluate the consistency between the registered records and subsequent publications with respect to outcomes and other data as well as to determine whether outcome-reporting bias favors significant primary outcomes. Methods: A systematic search of 15 registries was conducted from their inception to January 2014 to identify randomized clinical trials on acupuncture for which the status was listed as 'completed.' The subsequent publications were retrieved by searching PubMed and three Chinese databases. Basic characteristics and the registration information were extracted from the registered records and publications. We performed comparisons regarding primary outcomes and other data between the registered records and subsequent publications to assess the consistency and selective outcome reporting. Results: Eighty-eight trials on acupuncture with 96 published reports were identified. Only 19.3% (17/88) were registered before the start of the trial, suggesting prospective registration. The trial registration number was unavailable in 36 published reports (37.5%). A comparison of registered and published primary outcomes could be conducted in 71 publications (74.0%), and the inconsistency of the primary outcomes was identified in 45.1% (32 of 71); 71.4% (15 of 21) had a discrepancy that favored statistically significant primary outcomes, while 28.6% (6 of 21) favored nonsignificant primary outcomes. Furthermore, the other inconsistencies between the registry records and subsequent publications involved the inclusion criteria (54.7%), exclusion criteria (47.9%) and controls (22.9%). Conclusions: We find that prospective registration for randomized clinical trials on acupuncture is insufficient, selective outcome reporting is prevalent, and the change of primary outcomes is intended to favor statistical significance. These discrepancies in outcome reporting may lead to biased and misleading results of randomized clinical trials on acupuncture. To ensure publication of reliable and unbiased results, further promotion and implementation of trial registration are still needed

Zusanli (ST36) acupoint injection for preventing postoperative ileus : a systematic review and meta-analysis of randomized clinical trials

Objective: To evaluate the preventive effect of Zusanli (ST36) acupoint injections with various agents, for postoperative ileus (POI). Methods: We searched electronic databases for randomized controlled trials from inception to 1st February 2015 evaluating ST36 acupoint injection for preventing POI. Revman 5.2.0 was used for data analysis with effect estimates presented as mean difference (MD) with 95% confidence interval (CI). Statistical heterogeneity was tested using I 2 (defined as significant if I 2 > 75%). We used a random effects model (REM) for pooling data with significant heterogeneity. Results: Thirty trials involving 2967 participants were included. All trials were assessed as high risk of bias (poor methodological quality). For time to first flatus, meta-analysis favored ST36 acupoint injection of neostigmine (MD −20.70 h, 95% CI −25.53 to −15.87, 15 trials, I 2 = 98%, REM), vitamin B1 (MD −11.22 h, 95% CI −17.01 to −5.43, 5 trials, I 2 = 98%, REM), and metoclopramide (MD −15.65 h, 95% CI −24.77 to −6.53, 3 trials, I 2 = 94%, REM) compared to usual care alone. Meta-analysis of vitamin B1 favored ST36 acupoint injection compared to intramuscular injection (MD −17.21 h, 95% CI −21.05 to −13.36, 4 trials, I 2 = 89%, REM). Similarly, for time to bowel sounds recovery and first defecation, ST36 acupoint injection also showed positive effects

Ginseng for Alzheimer's disease : a systematic review and meta-analysis of randomized controlled trials

Background: There is no curative treatment for Alzheimer’s disease (AD). Ginseng is widely used in the treatment of AD in Asian countries. Objective: To evaluate the effectiveness and safety of ginseng for AD. Methods: We searched seven main databases for randomized clinical trials (RCTs) on ginseng for AD from their inception to December 2014. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.2 to synthesize the results. Results: Four RCTs involving 259 participants were identified for this systematic review. The methodological quality of included studies was not promising. All comparisons were made between combined treatment (ginseng plus conventional treatment) versus conventional treatment. The results of meta-analyses and several individual studies showed that the effectiveness of combined treatment was inconsistent as measured by MMSE, ADAS-cog, ADAS-noncog, and CDR. No studies reported the outcomes of quality of life (QoL). The current data did not report serious adverse events. Conclusion: This review showed that the effects of ginseng on AD were still inconclusive. The main limitations of the available studies were small sample sizes, poor methodological qualities and no placebo controls. Larger, well-designed studies are needed to test the effect of ginseng on AD in the future

Characteristics of clinical studies of summer acupoint herbal patching : a bibliometric analysis

Background: Summer acupoint herbal patching (SAHP) has been widely used in China for thousands of years. This bibliometric analysis aims to provide a comprehensive review of the characteristics of clinical studies on SAHP for any condition. Methods: We included clinical studies such as randomized clinical trials (RCTs), controlled clinical studies (CCTs), case series (CSs), case reports (CRs), and cross-sectional studies on SAHP for any condition. Six databases were searched from date of inception to March 2015. Bibliometric information and study details such as study type, characteristics of participants, details of the intervention and comparison, and outcome were extracted and analyzed. Results: A total of 937 clinical studies were identified and which were published between 1977 and 2015. This included 404 RCTs, 52 CCTs, 458 CSs, 19 CRs and 4 cross-sectional studies and involved 232,138 participants aged 2 to 90 years from two countries. Almost all studies were from China (936, 99.89 %). The five conditions most commonly treated by SAHP were asthma (401, 42.80 %), chronic bronchitis (146, 15.58 %), allergic rhinitis (117, 12.49 %), chronic obstructive pulmonary disease (73, 7.79 %), and recurrent respiratory tract infection (42, 4.48 %). Among 502 controlled studies, the majority compared SAHP alone with different controls (16 categories, 275 comparisons). The most commonly used controls were western medicine, placebo, traditional Chinese medicine, no treatment and non-pharmaceutical traditional Chinese therapies. Composite outcome measures were the most frequently reported outcome (512, 69.19 %). Conclusion: A substantial amount of research on SAHP has been published in China and which predominantly focuses on respiratory conditions. The findings from this study can be used to inform further research by highlighting areas of greatest impact for SAHP

Adjuvant intensity-modulated radiotherapy (IMRT) with concurrent paclitaxel and cisplatin in cervical cancer patients with high risk factors : a phase II trial

Objective To evaluate the safety and efficacy of adjuvant intensity-modulated radiotherapy (IMRT) with concurrent paclitaxel and cisplatin (TP) in early stage cervical cancer patients with high risk factors after radical hysterectomy. Methods Patients who underwent radical hysterectomy for FIGO stage IB-IIA cervical cancer and had high risk factors for recurrence were recruited. One cycle of TP was delivered before and after concurrent chemoradiotherapy, respectively. Concurrent chemoradiotherapy began 21 days after the start of the initial cycle of the chemotherapy with two cycles of TP delivered on day 1 and day 29 of radiotherapy. Primary endpoints were overall survival (OS) and relapse-free survival (RFS), with toxicities, local-regional control (LC) and distant failure (DF) rate as secondary endpoints. Results Between 2008 and 2012, 67 patients were evaluable. The 2 and 4-year RFS rates were 98.2% and 92.9%. Corresponding OS rates were 100%, and 98.0%, respectively. The 4-year LC and DF rates were 98.0% and 5.2%, respectively. Grade 3-4 acute leucopenia, neutropenia and thrombocytopenia occurred in 25.4%, 11.9% and 1.5% of patients, respectively. There were 89.6% and 59.7% patients experienced acute vomiting and diarrhea, but only 6.0% and 6.0% patients were grade 3, respectively. No case of chronic toxicity exceeded grade 2. Conclusion Adjuvant concurrent IMRT with paclitaxel plus cisplatin are safe and effective in early stage cervical cancer patients with high risk factors for recurrence following radical hysterectomy