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JKM > Volume 41(1); 2020 > Article
Jeung, Jeon, and Jo: Current Status of N-of-1 Trials for Herbal Medicine -Literature Review

Abstract

Objectives

To overcome the limitations of randomized controlled trials, many other trials design is tested. The n-of-1 trial is a promising research method in the field of Korean medicine because of this methodology can examine the optimal treatment for each patient strictly. Therefore, we reviewed the status of N-of-1 studies on herbal medicine.

Methods

A systematic literature review was conducted based on the pubmed database. The search term were ‘N-of-1 Trial’, ‘Chinese Medicine’, ‘Herbal Medicine’, ‘Kampo’. There was no restriction in year.

Results

Four clinical trials have been identified to demonstrate the effectiveness of herbal medicines for Kidney-yin-deficiency syndrome, bronchiectasis and gastric cancer. These studies suggest that the N-of-1 design is a study that encourages patient involvement, demonstrates the effectiveness of herbal medicines and helps reduce unnecessary medication.

Conclusion

The N-of-1 clinical trial may be a rigorous methodology suitable for the clinical setting and may help the development of evidence-based Korean medicine. Attention is also needed in this research method in Korea.

Fig. 1
ABAB design
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Fig. 2
Flowchart of review
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Table 1
Characteristics of N-of-1 Trials for Herbal Medicine
Citations Target disease Number of subjects Research design Inverventions Controls Evaluation Items Outcome Remarks
Yuhong H (2013) 18 Kidney-yin-deficiency syndrome N=50 ABABAB (24week) Liuweidihuang-wan Placebo Medication persistence, Kidney-yin-deficiency score, SF-36 There is no significant difference between Liuweidihuang-wan and placebo in patients with Kidney-yin-deficiency syndrome. Patients who responded clearly to Liuweidihuang-wan wanted to keep the medication. This study shows Liuweidihuang-wan, a representative treatment for Kidney-yin-deficiency, has not been shown to be effective for all Kidney-yin-deficiency patients. However, this results may be due to the limitation of diagnosis through Kidney-yin-deficiency score,.
Huang H (2014) 19 Bronchiectasis N=3 ABABAB (12–18 week) In addition to the controls
Lung-Spleen-Qi-Deficiency(肺脾氣虛) : Codonopsis pilosula(黨參), Pericarpium Citri Reticulatae(陳皮), Rhizoma Atractylodis Macrocephalae(朮)
Qi-yin-deficiency(氣陰 證) : Radix Adenophorae (南沙參), Radix Glehniae (北沙參), Radix Rehmanniae Recens (生地黃)
Phleigm-heat(痰熱) : Scutellaria baicalensis(黃芩), Herba Violae(紫花地丁)
Radix Lithospermi (紫草) 15 g, Rhizoma Fagopyri Cymosi (金蕎麥) 30 g, Radix Ophiopogonis(麥門冬) 15 g, Poria cocos(茯苓) 15 g, Radix Astragali (黃芪) 20 g, Rhizoma Bletillae (白芨) 10 g, Platycodon grandiflorum (朮) 10 g, Semen Coicis (薏苡仁) 30 g. Symptom score, expectoration volume. Syndrome-differentiation based administration did not show any significant difference in patients with bronchiectasis. These study shows that syndrome-differentiation based administration has statistically significant effects.
These results may be due to the limitation of the syndrome-differentiation approach used in this study.
Huang H (2018) 20 Bronchiectasis N=17 ABABAB Or ABAB (24week) Symptom score, expectoration volume, COPD Assessment score(CAT) In patients with bronchiectasis, syndrome-differentiation based administration showed a statistically significant but clinically insignificant effect compared to the controls. There was a clear statistical difference compared to the prior small study.
Li J (2019) 21 Gastric Cancer N=6 ABABAB or ABAB 20–30 weeks) In addition to the controls
Astragalus mongholicus (黃芪) 120 g, Semen Cuscutae (菟絲子) 60 g
Radix Pseudostellariae (太子參) 45 g, Rhizoma Atractylodis Macrocephalae (朮) 45 g, Rhizoma Zingiberis (乾薑) 45 g, Radix Glycyrrhizae Preparata (炙甘草) 45 g, Rhizoma Pinellinae Praeparata (法半夏) 15 g, Fructus Amomi (砂仁) 15 g, Rhizoma Dioscoreae (山藥) 60 g, Lignum Millettiae (鷄血藤) 60 g. WBC count, Quality of Life Astragalus and Semen Cuscutae were able to improve white blood cell reduction by chemotherapy in gastric cancer. These study shows that addition of Astragalus and Semen Cuscutae is effective on white blood cell reduction.
However, results from fewer subjects are a limitation in generalizing results. It is necessary to identify which patients respond by this treatment.

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