Study On The Dose - Effect Relationship Of Traditional Chinese Medicine Prescriptions Based On Semi - Structured Interviews And Multi - Stage Random Questionnaires

Wang Qingren in Qing dynasty pointed out number of Chinese herbs in a prescription was important, but more important was the doses of these herbs. Reading medical records, some cases in severe and intractable conditions were treated by large doses of Chinese herbs, while some were treated only in a small dosage. The efficacy was both satisfactory. Clinical doses of Chinese herbs in the same formula are greatly varied by different traditional Chinese medicine (TCM) practitioners; even the doses of Chinese heros in same formula by the same TCM practitioner will change due to different conditions. There is a saying that the mystery of TCM is the dose of Chinese herbs. At present, misunderstanding and confusion are still existent in the research of dose-effect relationship in TCM formula/herb(s) and inheritance of herbal dosage. Insufficient dosage of formula/herb(s) impedes the improvernent of therapeutic effect, while application of large dosage in blind way can also bring about potential risk of herbal safety. Research on dose-effect relation has become an academic key issue in TCM. A dose-effect research group led by professor Tong Xiaolin expects to clarify the relationship between dose and effect in multi-dimensional aspects like literature review, experiment, and clinical trial, etc. together with modem scientific and technological methods such as systems biology, analytical chemistry, philology, and bioinformatics and so forth. As a member of the group, from the perspective of evidence-based medicine (EBM). dose-effect relation of formula/herb(s) has been investigated by semi-structured interview and multi-stage randomized questionnaire.ObjectiveThe study aims to comb dose-effect relation of formula/herb(s), experience of applying special dosage of herb(s) or in fixed ratio, principles of clinical dosage of herb(s), and control strategies of dosage in clinical application, probe into their scientific connotations, and perfect an individual-oriented theory on herbal dosage of formula/herb(s) by semi-structured interviews on national top physicians and multi-stage randomized questionnaires on TCM clinical practitioners.In addition, by introducing framework analysis, a qualitative research method, the study is going to carry out methodology exploration in TCM field especially at the aspect of dose-effect relation.ContentsFirst of all, national top physicians were selected for semi-structured interviews. Their opinions on influence factors of dose-effect relation of formula/herb(s), control strategies of adverse reactions due to large dose of herb(s) or toxic herb(s), and views on dosages of prepared herbs stipulated in Chinese pharmacopoeia (2010edition) were summarized and extracted in order to provide empirical support for current TCM practitioners on their clinical application and expert guidance for amendments of Chinese pharmacopoeia in future.Secondly, by multi-stage randomized questionnaire, the doses of50frequently-used Chinese herbs in current TCM practitioners’ clinical applications were calculated and a comparison between these doses of Chinese herbs and stipulated doses of the corresponding Chinese herbs in pharmacopoeia was made for the goal of providing reference for amendments of pharmacopoeia in future.Thirdly, instructions on how to decoct and take by current TCM practitioners were collected in order to sum up the laws of decocting method and instructed administration by questionnaire investigation.Finally, through questionnaire investigation, influence factors of dose-effect relation were clear and a sequence of the selected factors according to the significance in clinical practice was accomplished, and influences on herbal dosage by other factors like gender, age, location of practicing TCM, professional title, education background, and years of engaging in TCM career, etc. were also discussed.MethodsIn the part of interview,9national top physicians were agreed on acceptance of semi-structured interviews and observation method was also included. Snowball sampling, an approach of purposive sample, was applied to select the appropriate national top physicians. The transcription data were analyzed by framework analysis. The interview manuscripts were coded, classified, and extracted by qualitative software ATLAS.ti.In the part of questionnaire investigation, multi-stage randomized sampling was adopted. To be specific, according to the specific administrative regions in China, all provinces and autonomous regions can be classified into7plates including North China, Northeast. East China, Central China, South China, Southwest, and Northwest. One province or autonomous region was chosen from the7plates by random number table, and7provinces of Jiangsu, Guangdong, Henan, Shanxi, Jilin, Guizhou and Gansu were picked out. Two thousand three hundred and ninety one comprehensive TCM hospitals in China were categorized into the corresponding provinces or autonomous regions. Five hospitals were selected from each above-mentioned province by random number table. Finally,10practitioners at most meeting the criteria were selected from each TCM hospital by random number table. However, if number of practitioners at county-level of TCM was less than10, then all of them would be included.In the process of questionnaire analysis, t test, non-parametric test, frequency statistics, and multiple choice sorting, etc. were applied.ResultsNine national top physicians were interviewed and303effective questionnaires were collected and analyzed.Through analysis of interview manuscripts from national top physicians and multi-stage randomized questionnaire, some results were obtained.(Ⅰ) Control strategies of adverse reactions due to large dose of herb(s) included making differentiation of disease conditions, available in emergency and severe disease, reducing dosage in time or changing to pill, ointment, tea soup when disease tendency has alleviated and healthy qi recovered, drawing on predecessor’s clinical experience, appropriate herbal combination, and symptomatic treatment or detoxication therapy like taking hydromel or sweet mung bean soup, even with the combination of western medicine when adverse reaction occurs.(Ⅱ) Control strategies of adverse reactions of toxic hcrb(s) contained prescribing in large dosage without any hesitation if disease condition warranted, starting from a low dosage and gradually increasing dosage if it is ineffective, decocting first and for a long time, adding herb with actions of counteracting toxicity of another herb, and herbal combination.(III) In comparison with these herbs in the upper limited value (ULV) of doses stipulated in pharmacopoeia, the median in32Chinese herbs exceeded the ULV stipulated in pharmacopeia accounting for57.14%(32/56). There were17Chinese herbs with5g more than the ULV stipulated in pharmacopeia in comparison with the corresponding medians, including semen ziziphi spinosae (suan zao ren), rhizoma chuanxiong (chuan xiong), rhizoma atractylodis macrocephalae (bai zhu), poria (fu ling), semen persicae (tao ren), radix rehmanrtiae (sheng di huang), radix rehmanniae praeparata (shu di huang), bulbus fritillariae thunbergii (zhe bei mu), fructus gardeniae (zhl zi), fructus trichosanthis (gua lou), herba artemisiae scopariae (yln chen), fructus evodiae (wu zhu yu), fructus schisandrae chinensis (wu wei zi), radix bupleuri (chai hu), radix paeoniae alba (bai shao), radix ct rhizoma ginseng (ren shen), and rhizoma alismatis (ze xie).(Ⅳ) There were32Chinese herbs which were prescribed by over50%of the selected TCM practitioners who exceeded ULV stipulated in Chinese pharmacopeia, accounting for57.14%(32/56).9Chinese herbs including fructus evodiae (wii zhu yu), radix ophiopogonis (mai dong). fructus schisandrae chinensis (wu wei zi). rhizoma coptidis (huang lian). rhizoma atractylodis macrocephalae (bai zhu). radix angelicae sinensis (dang guI). rhizoma pinelliae (ban xia). radix et rhizoma ginseng (ren shen). and rhizoma alismatis (ze xie) which were used by over80%of the participated TCM practitioners in comparison with those in the pharmacopeia.(Ⅴ) One third participated TCM practitioners believed that the current dosage of Chinese herb has become larger and larger. Over half practitioners deemed that it was not a universal phenomenon of dosage increasing, and only some TCM practitioners increased dosage. The reason for dose increase was principal quality reduction of Chinese herbs.(Ⅵ) The number of Chinese herbs in a prescription by current TCM practitioners was9to16accounting for92.08%.(Ⅶ) With regard to method of decocting and taking, over half practitioners selected the choice saying decocting twice, mixing together, and taking in several times. Take internal injury and miscellaneous disease for example, it took51.47minutes on average to decoct in twice calculating after soup is boiling. When talking about the most appropriate water addition, the ratio of weight of Chinese herbs and quantity of water was1to5or6in the first decoction, that’s to say,100grams of Chinese herbs need500to600milliliter water. In the second decoction, the ratio was1to2. During investigation, some TCM practitioners didn’t tell patients how to decoct and take medicine.(Ⅷ) The top3influence factors on dose-effect relation were variety and quality of Chinese herbs, preparation, and herbal combination. What’s more. it was also related to practitioner’s gender, age. location of practicing TCM. professional title. education background, and years of engaging in TCM career. In addition, stipulation of prepared herbal dosage in Chinese pharmacopeia also has certain influence on dose-effect relation.(Ⅸ) Authority and normalization of Chinese pharmacopeia as a code in the field of TCM should be abided by. But, the dosages of herbs with neutral property could be broadened.ConclusionIt is closely related between dose and effect by framework analysis. The dose in the study mainly includes current herbal dosage of Chinese herbs and stipulated dose of prepared Chinese he(?)bs in pharmacopoeia. The former in prescription is partly restricted by the latter, but the discrepant condition always occurs. As regard to effect, influence factors and safety control strategies of Chinese herbs are included. Any obtained effect must be at premise of safety. Influence factors are extremely important on obtaining effect. The stipulation of prepared herbal dosage in Chinese pharmacopeia is also an influence factor of dose-effect relation.The doses of Chinese herbs in clinical practice by different TCM practitioners were uncertain and variable. Compared with the stipulated doses in pharmacopoeia, the real doses of the corresponding herbs prescribed by TCM practitioners mostly were larger. It is suggested that herbal dosage in Chinese pharmacopeia be listed in clinical medicine guidelines of the People’s Republic of China acting as reference not hard-and-fast rules.