COMMISSION E: EVALUATION METHODS AND CRITERIA

VII. COMMISSION E: EVALUATION METHODS AND CRITERIA

Unlike the FDA drug reviews in which data are passively submitted for evaluation by the manufacturer, members of Commission E actively collect and review data, both published and unpublished, from various sources, including from:

Traditional sources Experimental, pharmacological, and toxicological studies Clinical studies Field and epidemiological studies

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Patient case records from physicians’ files Unpublished proprietary data submitted by manufacturers

Clinical data are reviewed to ensure that the herbal medicines are reasonably safe when used according to the dosage, contraindications, and other warnings provided in the monographs. With regard to efficacy, the Commission is guided by ‘‘the doctrine of reasonable certainty. The Com- mission will grant a positive review if the scientific data provided reasonable verification of a particular historical use.’’ Thus some of the older herbs were given positive reviews despite the absence of a significant body of clinical studies. Since 1990, the Commission began to focus on good clinical practice studies to document the uses and have amended usage to a more restricted indication. An example is the Hawthorn (Cratageus) monograph of 1984, which initially contained indications for use in Stages I and II of the New York Heart Association (NYHA). This indication was limited in July 1994 for Stage II NYHA and only for hawthorn leaf with flower. Clinical studies using other parts of the hawthorn plant made individually from berry, leaf, or flower failed to show sufficient efficacy. These individual parts are, however, still sold as ‘‘traditionally used herbal products.’’

Unapproved herbs with negative evaluations are those where no plausible evidence of efficacy was available or where safety concerns outweigh the potential benefits. Even products with minor risks were eliminated if they are not balanced by an acceptable benefit. Negative monographs were also given to herbs with no traditional usage or for which there are no clinical or pharmacological studies. Herbs that pose a risk were withdrawn immediately and those unapproved drugs that do not pose a health risk can be sold in the German market only until 2004. Unapproved drugs with specified risks include angelica seed (photosensitivity caused by coumarins), ergot (wide spectrum of activity), hound’s-tongue (hepatotoxic pyrrolizidine alkaloids), nutmeg (psychoactive and abortifacient effect in large doses), lemongrass (toxic alveolitis), and yohimbine (anxiety hypertension and tachycardia).

VIII. TRADITIONAL CHINESE HERBS The pharmacopoeia of traditional Chinese herbs includes the richest and

oldest sources of medicinal plants. Herbal medicines have been used for millennia in China and one of the earliest texts is the Shen Nong Ben Cao Jing published in 101 B.C . Each subsequent emperor and dynasty has continued to commission written pharmacopoeia on medicinal herbs. One of the most prominent texts, Ben Cao Gang Mu, first published in the Ming dynasty in the late 1500s, is still a reference source for current TCM practitioners. This text contains 52 volumes and includes 1160 drugs from plants and 11,096

Criteria for Use of Herbal Medicine 83

prescription formulae. This detailed pharmacopoeia, written by Li Shih Chen, has botanical drawings of plants drawn by his son. In 1596, it was translated into Latin and later into English, French, German, Russian, and Japanese. Sadly, since then the Chinese materia medica has not been improved for hundreds of years and current TCM practices do not differ much from that of the sixteenth century. Very little modern safety and efficacy data are known for the vast majority of TCM products. What exists are in the Chinese language, and archaic nonphysiological concepts like yin, yang, coolness, dampness, ‘‘heatness,’’ wind, and qi are used. The description of organs like lung, spleen, and kidney does not correlate with their modern anatomical meanings. These factors coupled, with the general problems in herbal medicines outlined earlier, prevent the acceptance of TCM into mainstream medical practice, despite their popularity as food supplements.

A. The Way Forward for TCM Nevertheless it cannot be denied that this ancient Chinese materia medica

harbors many potentially lifesaving bioactive compounds. The isolation of the important antimalarial drug artemesinin from the Chinese herb Qing hao su (Artemesia annua) is a case in point. The modernization of the TCM industry and its acceptance into mainstream medical practice will depend on how the industry addresses the problems of

Unauthenicated botanical raw material Unknown mechanisms of action Unknown bioactive compounds Nonstandardization of herbal products with respect to active ingre-

dients Poor manufacturing practices Lack of toxicology and safety data Lack of randomized controlled trials to demonstrate efficacy

One way forward could be the adoption of the modified German Commission E system. Here the emphasis is first on the use of authenticated raw materials, and the standardization of agricultural, processing, and storage practices. The chemical components of many herbs are increasingly being elucidated. What is important is that their mechanisms of action be clarified using modern cell and molecular biology techniques. In this regard, the advent of microarray technology and the ability to examine many protein targets and signaling systems simultaneously are ideally suited for herbal research as herbs contain multiple compounds with potentially many modes of action. The introduction of good manufacturing practices will result in herbs with standardized bioactive components. The pharmacodynamics,

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pharmacokinetics, safety, and efficacy of bioactive compounds can be exam- ined scientifically in animal models. Finally, these herbal products can be tested in human studies where the outcome parameter can be refined accord- ing to the mechanisms of action defined in vitro and in animal models. The complete process will take many years and will be expensive. Here an enlightened and practical attitude on the part of legislators and regulators will help the industry move forward. Funds for research will have to be set aside from industry. Exclusive marketing rights for products that have been certified will help manufacturers recoup the costs of research and product standardization. Such a system has already been suggested by the U.S. FDA’s guidance document for industry on botanical drug products (45). As in the German system, the first emphasis should be on manufacturing quality and standardization of bioactive components. Safety has to be assured in the recommended doses. Efficacy can be based partly on traditional usage, especially of herbs that are commonly consumed. In this way over the years herbal medicines will achieve the same recognition as pharmaceutical drugs. Their promise of safety and efficacy can then be fulfilled.

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