Chung-Wah Cheng

Efficacy of a Chinese herbal proprietary medicine (hemp seed pill) for functional constipation

OBJECTIVES:Functional constipation (FC) is a common clinical complaint. Despite a lack of consolidated evidence, Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. The aim of this study was to assess, with a rigidly designed study, the efficacy and safety of a CHM proprietary medicine, Hemp Seed Pill (HSP), in optimal dosage for treating FC.METHODS:This study comprised two parts: trial I, a dose determination study, and trial II, a placebo-controlled clinical study. In trial I, the optimal dosage of HSP was first determined from among three doses (2.5, 5.0, and 7.5 g b.i.d.). In trial II, a randomized double-blind study, the efficacy and safety of HSP for FC patients (Rome III criteria) in excessive syndrome as defined by traditional Chinese medicine (TCM) theory were compared with placebo. All participants in trials underwent a 2-week run-in, an 8-week treatment, and an 8-week follow-up. The primary end point was the responder rate for complete spontaneous bowel movement (CSBM) during treatment. Participants with a mean increase of CSBM ≧1/week compared with their baselines were defined as responders. Secondary outcome measures included responder rate during follow-up, individual and global symptom assessments, and reported adverse effects (AEs).RESULTS:The dose of 7.5 g b.i.d. showed better therapeutic effect than that of 2.5 and 5.0 g b.i.d. among 96 subjects (32 per arm) in trial I and was therefore selected for comparison with placebo in trial II. In trial II, 120 subjects were randomized into two arms (60 per arm). Responder rates for the HSP and placebo groups were 43.3 and 8.3% during treatment and 30.0 and 15.0% in the follow-up period, respectively (P<0.05). Those in the HSP group showed benefit in terms of increased CSBM, relief in the severity of constipation and straining of evacuation, and effective reduction in the use of rescue therapy when compared with placebo. No serious AE was reported.CONCLUSIONS:HSP (7.5 g b.i.d.) is safe and effective for alleviating FC for subjects in excessive syndrome. Optimal dose determination may be crucial for all CHM studies.

Impact of psychological stress on irritable bowel syndrome.

Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.

Consolidated standards of reporting trials (CONSORT) for traditional Chinese medicine: current situation and future development

The reporting standards for randomized controlled trials were first published in 1996 by a group of scientists under the name “CONSORT,” which means consolidated standards of reporting trials. Revisions followed in 2001 and 2010. A draft of the CONSORT for traditional Chinese medicine (TCM) was published in both Chinese and English in 2007. After publication of the draft, comments were solicited from the medical community. Some papers did raise concerns about which items should be included in the CONSORT for TCM such as the rationale of the trial design, intervention, outcome assessment, and adverse events. We have now reached the next step which is the finalization of the CONSORT for TCM. Three tasks remain. First, the major changes in CONSORT statement 2010 should be integrated into the CONSORT for TCM. Second, Chinese drugs from minerals and animals should be included in the guidelines. Finally, agreement must be reached among the working groups. Once the draft is finalized, wide dissemination and co-publication will be considered.

Extending the CONSORT Statement to moxibustion

The STandards for Reporting Interventions in Clinical Trials Of Moxibustion (STRICTOM), in the form of a checklist and descriptions of checklist items, were designed to improve reporting of moxibustion trials, and thereby facilitating their interpretation and replication. The STRICTOM checklist included 7 items and 16 sub-items. These set out reporting guidelines for the moxibustion rationale, details of moxibustion, treatment regimen, other components of treatment, treatment provider background, control and comparator interventions, and precaution measures. In addition, there were descriptions of each item and examples of good reporting. It is intended that the STRICTOM can be used in conjunction with the main CONSORT Statement, extensions for nonpharmacologic treatment and pragmatic trials, and thereby raise the quality of reporting of clinical trials of moxibustion. Further comments will be solicited from the experts of the CONSORT Group, the STRICTA Group, acupuncture and moxibustion societies, and clinical trial authors for optimizing the STRICTOM.

Transparently reporting adverse effects of traditional Chinese medicine interventions in randomized controlled trials.

Although all Chinese materia medica (CMM) come from nature, CMM interventions have both therapeutic effects and adverse effects (AEs). Normally, AEs in randomized controlled trial (RCT) with traditional Chinese medicine (TCM) could be divided into five types as follows: 1) AEs under proper TCM principles and guidelines, such as the toxicity (acute and chronic) and allergy; 2) AEs due to improper usage without following TCM principles, involving without following the TCM therapeutic principles, over-dosage, improper processing and preparation methods, improper formula strategy, etc; 3) AEs due to contamination in CMM, such as heavy metal and pesticides contaminations in Chinese herbal medicine interventions, and intentional or unintentional contamination with drug(s); 4) AEs due to replacement of CMMs; 5) AEs due to drug-herb interaction. AEs of TCM should be treated properly. Overestimation or underestimation about AEs of TCM intervention will bring a wrong message to patients and health care providers. In order to give readers a more comprehensive understanding about the safety issue of study intervention, Consolidated Standards of Reporting Trials (CONSORT) for TCM should involve the background information on side effects of each CMM constituents and/or the study intervention, specific outcome assessment on AEs, the details of reported AEs and the interpretation of the AEs occurrence in a structural RCT report.

CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration.

Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized controlled trials (RCTs) of CHM formulas is disappointing, although CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions are available. A group of TCM clinical experts, methodologists, epidemiologists, and editors has developed this CONSORT Extension for CHM Formulas (CONSORT-CHM Formulas 2017) through a comprehensive process, including publication of the draft version, solicitation of comments, revision, and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist subitem, keywords, was added to facilitate indexing and data searching. Seven of the 25 CONSORT checklist items, namely title and abstract, background and objectives, participants, interventions, outcomes, generalizability, and interpretation, are now elaborated, and the explanation of harms specific to CHM formulas is revised. Illustrative examples and explanations are also provided. The group hopes that CONSORT-CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas.Chinese herbal medicine (CHM) formulas are the major components of traditional Chinese medicine (TCM) interventions. The general reporting quality of randomized controlled trials (RCTs) of CHM formulas is disappointing, although CONSORT (Consolidated Standards of Reporting Trials) Statement extensions for herbal medicinal interventions and acupuncture interventions are available. A group of TCM clinical experts, methodologists, epidemiologists, and editors has developed this CONSORT Extension for CHM Formulas (CONSORT-CHM Formulas 2017) through a comprehensive process, including publication of the draft version, solicitation of comments, revision, and finalization. The CONSORT 2010 Statement was extended by introducing the idea of TCM Pattern and the features of CHM formulas. One new checklist subitem, keywords, was added to facilitate indexing and data searching. Seven of the 25 CONSORT checklist items, namely title and abstract, background and objectives, participants, interventions, outcomes, generalizability, and interpretation, are now elaborated, and the explanation of harms specific to CHM formulas is revised. Illustrative examples and explanations are also provided. The group hopes that CONSORT-CHM Formulas 2017 can improve the reporting quality of RCTs of CHM formulas.

Appropriately Selecting and Concisely Reporting the Outcome Measures of Randomized Controlled Trials of Traditional Chinese Medicine

Evaluating outcome is the primary means by which different medical modalities can be compared with regard to effectiveness. In traditional Chinese medicine (TCM), this focus has prompted practitioners to search for outcome measures that can objectively verify the effectiveness of TCM interventions, especially in the context of randomized controlled trials (RCTs). Commonly used indexes for outcome assessment in RCTs of TCM can be categorized into two types: TCM-specific outcomes such as tongue and pulse characteristics, and Western medicine (WM)-specific outcomes such as blood test and X-ray examination results. Some studies include both types of indicators. During the trial design, it is necessary to consider the rationales of selecting outcome assessments, the purpose and study approach, balance between objective and subjective indexes, standardization of outcome assessment, and standardized outcome indexes. We recommend to report the outcome assessment in RCTs of TCM in the following format: 1) identifying the primary and secondary outcomes based on the purpose and hypothesis of the trial; 2) defining the primary and secondary outcomes clearly; 3) presenting the rationale of selection; 4) presenting the method with aims to standardize the assessment process; 5) presenting the method to improve the reliability of assessment; and 6) stating the termination criteria in the trial.

The Quintessence of Traditional Chinese Medicine: Syndrome and Its Distribution among Advanced Cancer Patients with Constipation

Constipation is a common problem in advanced cancer patients; however, specific clinical guidelines on traditional Chinese medicine (TCM) syndrome (Zhang) are not yet available. In this cross-sectional study, the TCM syndromes distribution and their common symptoms and signs among 225 constipated advanced cancer patients were determined. Results showed that 127 patients (56.4%) and 7 patients (3.1%) were in deficient and excessive patterns, respectively, while 91 patients (40.4%) were in deficiency-excess complex. The distributions of the five syndromes were: Qi deficiency (93.3%), Qi stagnation (40.0%), blood (Yin) deficiency (28.9%), Yang deficiency (22.2%), and excess heat (5.8%). Furthermore, age, functional status, and level of blood haemoglobin were factors related to the type of TCM syndrome. A TCM prescription with the functions on replenishing the Deficiency, redirecting the flow of Qi stagnation and moistening the dryness caused by the blood (Yin) deficiency can be made for the treatment of advance cancer patients with constipation. Robust trials are urgently needed for further justifying its efficacy and safety in evidence-based approaches.

Precise reporting of traditional Chinese medicine interventions in randomized controlled trials.

Traditional Chinese medicine (TCM) intervention should be concisely and precisely reported in randomized controlled trials (RCTs). Based on State Food and Drug Administrations categories, we recommend reporting the interventions as follows: (1) Single Chinese herbal medicine-based/formula-based/extraction-based intervention includes 1) Name, dosage format and registration; 2) The composition and quality of intervention; 3) Pharmaceutical processing and quality control; 4) Stability of final product and quality control; 5) Function and safety description; 6) Dosage and treatment course; 7) Control group. (2) Active compound-based TCM drug intervention includes 1) Name of active compound(s); 2) Original source of active compound(s); 3) The brief process obtaining active compound(s); 4) Percentage of active compound(s) in final product; 5) Added materials and its quality and quantity control. Besides, the detailed information of intervention can be published as an online supplement in web site.

Consensus-based recommendations for case report in Chinese medicine (CARC)

Case reports are valuable clinical evidence in traditional Chinese medicine (TCM). However, the general reporting quality is suboptimal. A working group comprising 20 members was set up to develop systematic recommendations on case report in Chinese medicine (CARC). The working group (CARC group) developed a primary checklist based on reviewing the general reporting quality of case reports in TCM and thorough internal discussion. Two-round consensus process had been carried out among clinical experts, evidence-based medicine methodologists, medical journal editors and clinical practitioners with designated questionnaire embedded with the primary checklist. In total, 118 participants from 17 provinces of China and Korea completed the questionnaires. Their feedback was analyzed and discussed by the CARC group. The checklist was amended accordingly, and the final version, comprising 16-item, is presented here. Under the framework of CARC recommendations, the reporting quality of case reports in TCM can be improved.