1明晰报告中医药随机对照试验中中药的毒副作用【摘要】 中药虽取诸天然，但亦可含对人体有害的物质，因此，近年来中药的毒副作用越来越受到关注。中药毒副作用可以分为不可预期类、使用不当类、中药“污染”类、品种混乱类和中西药物相互作用类等。使用不当类包括处方不遵从中医药理论、过量使用、炮制及制剂方法不当和配伍不当等；中药“污染”类包括重金属、农药残留及中药产品被化学药物成分“污染” 。中药的毒副作用，必须明晰报告。过高或过低估计中药的毒副作用，都会误导临床医生及患者。我们建议在中医药随机对照试验报告规范中，报告副作用时，应包括以下方面：研究药物毒副作用的背景资料、针对副作用的特异性结局评估指标；毒副作用的详细内容及其诠释。 【关键词】 中医学 中药 临床研究 随机对照试验 循证医学1 IntroductionIt is generally accepted that all health interventions, including traditional Chinese medicine (TCM), should be as safe as possible prior to adopting them in clinical practice. There is a common misconception that herbal materials - including those used in TCM, known as Chinese materia 2medica (CMM) are harmless to humans because they come from natural sources 1. In fact, TCM may cause serious adverse effects (AEs) when adulterated or used incorrectly. Although the potential toxicity of specific CMM interventions has attracted more attention worldwide as the use of herbal interventions increases 2, 3, most researches on TCM continue to focus almost exclusively on establishing efficacy and effectiveness. Our previous study reported that only 30% of randomized controlled trials (RCTs) of TCM reported AEs, and most of them were too vague on this topic for readers to appropriately determine the safety of the TCM interventions studied. Better reporting on AEs in RCTs of TCM is therefore required.The Draft Consolidated Standards for Reporting Trials of Traditional Chinese Medicine (CONSORT for TCM) were published in Chinese and English in 2007 4, 5 to solicit feedback from experts in different specialties. In that draft, one checklist item addressed the reporting of safety of TCM interventions. Upon further consideration, it became apparent that a single checklist item to address the issue of safety was not enough. The extension of the CONSORT 3statement on reporting of harm 6 has addressed how to illustrate the AEs in RCT of Western pharmaceuticals. Since it is essential to transparently illustrate the AEs of RCTs for all interventions, including those used in TCM, this article aims to enhance awareness of safety issues for TCM interventions by promoting improved reporting by 1) summarizing the types of AEs reported with TCM; 2) examining the impact of AEs on RCTs with TCM; and 3) formulating the reporting structure. The corresponding revisions of the draft CONSORT for TCM are also recommended.2 Types of AEsCMM products used in TCM can refer to materials of herbal, animal or mineral origin. Normally, AEs associated with CMM products used in TCM could be divided into five types as follows.2.1 Unpredictable AEs Theoretically, TCM interventions are prescribed by clinical practitioners according to the golden principle of treatment based on syndrome differentiation. Even if this principle is followed, AEs cannot be entirely 4avoided, and toxicity (acute or chronic) or allergic reactions may occur. For example, Caulis Aristolochia manshuriensis (Guanmutong) is a commonly used Chinese herb in clinical practice, and has attracted attention for its significant nephrological toxicity in the last two decades 79 . The major compound in C.A. manshuriensis, aristolochic acid, induces acute tubular necrosis in the kidney, thus resulting in significant toxicity. But based on the Chinese medicine theories, it cannot be predicted. Allergy is another AE associated with the usage of TCM interventions 10 including allergic shock, allergic asthma and allergic purpura. Although a previous history of allergy to herbs can remind the practitioner to be careful, this knowledge is of little value for patients who have not previously been exposed to these allergens.2.2 AEs arising from improper use TCM drug must be used according to TCM principles, and improper usage may result in AEs. Typically, improper usage involves 1) prescription without following the TCM therapeutic principles; 2) overdosage; 3) improper processing and preparation methods; 4) improper formulas.5Firstly, prescriptions should be based on the TCM treatment principles. If these principles are not obeyed, potentially efficacious interventions may produce AEs. For example, Rhizoma Coptidis (Huanglian) is very cold in nature and bitter in taste. Used properly, it can clear heat, dry dampness, drain fire and expel toxicity. Used improperly, it may damage the spleen and stomach resulting in nausea, vomiting, stomachache and loss of appetite in the short term; over the long term, improper usage may result in spleen qi deficiency. If the TCM theories are strictly followed, these AEs could be avoided.Secondly, overdosage is another common reason for AEs with TCM intervention. For example, most AEs related to the root of Herba Asari (Xixin) are because of high dosages. Traditionally, the limitation of daily dosage of H. Asari is less than 3 grams, although debate exists on this topic 11 . Another typical case of overdosage is Herba Ephedra (Mahuang). Although there is no clinical evidence f