Developing a Practical Methodology for Chinese Medicine Research --- Approach, Challenges and Solutions.

摘要

The purpose of the research is to develop a practical methodology to obtain convincing evidences in quality, safety and efficacy of Chinese Medicine. When we use evidence-based research methodology to prove the quality, safety and efficacy, we are facing many challenges.;The general perception that herbal drugs are very safe and free from side effects is not true. Little do they know in the modern conditions, that the current herbs used for preparation of traditional Chinese medicine have been very different as compared with the ancient herbs in planting, extracting, producing, storage, application, dose level and the duration of clinical use. The active ingredients of herbal formula are higher after extracting with modern scientific methods; and the toxicity may also be correspondingly higher. The potential side effects after long-term use should not be overlooked.;The quality control of Chinese herbal medicine is a systematic procedure. The initial critical step is to standardize the starting raw herbs, for knowing the exact species and subspecies, the ideal growing location, environmental conditions, harvesting methods, and storage conditions etc., i.e., following Good Agriculture Practice (GAP) to ensure the quality of the raw materials. The second step is to standardize the processing methods of the raw herbs. The third step is to standardize the preparation procedure of the final products according to the requirements of Good Manufacture Practice (GMP) guideline. The fourth step is to qualitatively and/or quantitatively evaluate the quality of the TCM medication based on one or more selected chemical markers.;The effect of Traditional Chinese Medicine (TCM) may be characterized by its chemical compounds, which are also the active ingredients. The reproducibility and the stability of the active ingredients are the foundation to ensure the efficacy of TCM. The safety and efficacy of TCM is evaluated through its pharmacological effects and in clinical studies. Many Chinese herbal medicines have a long history of traditional use. However, most of them are of unproven efficacy by today's standard. Well-designed randomized controlled trials and comprehensive pre-clinical studies are not known. Although the lack of qualified evidence does not mean that Chinese herbal medicines lack efficacy or are unsafe, properly designed experimental and clinical investigations should still be done today. There is a need to scientifically prove and clinically validate its safety and efficacy through chemical standardization, biological assays, and clinical trials.;The distinctiveness of Chinese medicine is manifested in the diversity and the complexity of its components, the instability of its quantity, the fuzziness of its action mechanism, and the uncontrollability of its producing process. Traditional Chinese herbal formulae are usually formed by more than one plants, animal or mineral items. The composition is extremely complex. The efficacy thus can hardly be guaranteed. The methods of harvesting, drying, storage, transportation, and processing of plant material influence the efficacy and safety. The consistent efficacy, therefore, can hardly be guaranteed. For thousands of years, it has been observed by clinical practice that Traditional Chinese Medicine (TCM) has a rich scientific connotation and has developed a unique healthcare system. However, variable sources of raw materials, unknown active ingredients, difficulties in quality control, lack of safety evaluation, unclear mechanism of action, etc., all these factors constitute major challenges in modernization of TCM.;Chemical analyses, biological assays, and animal experiments provide important fundamental information of Traditional Chinese Medicine. In modern biomedical research, they should also be necessary prerequisites for clinical trials. A Chinese herbal formula, no matter how effective and safe in the pre-clinical studies, cannot be assumed clinically valid. No marketing approval should be granted without clinical studies. Thus, clinical trial plays a decisive role in the research and development of Traditional Chinese Medicine. Currently the highest level of efficacy evidence is obtained from randomized controlled clinical trial. Thousands of years of traditional use can provide us with valuable guidelines to the selection, preparation and application of herbal formulations. To be accepted as viable alternatives to western medicine, the rigorous methods of scientific and clinical validations must be applied.;In conclusion, the methodology of Chinese medicine research needs to improve. One practical way is to apply the efficacy-driven approach through the following steps: i) getting a simple herbal formula to try solving a difficult clinical problem and start an evidence-based clinical trial using methodology acceptable to current standard clinical trials i.e. randomized, placebo-controlled; ii) parallel laboratory experiments to understand the mode of action should be done; and; iii) making sure that the quality of herbs and their extracts are of the best standard. A promising item shown in the clinical trial and laboratory experiments would deserve more pharmacological investigations before considering marketing. (Abstract shortened by UMI.)