Randomised controlled trial (RCT) has been regarded as the gold standard in the design of clinical trials due to its unique strength in minimising selection bias. However, the cultural and philosophical differences between Chinese Medicine and Western medicine pose practical challenges in designing RCTs that can demonstrate the effectiveness while being acceptable to both Chinese Medicine clinicians and the broader scientific community. Over the past decade (2014–2023), nearly 20,000 research outputs in the field of Chinese Medicine have included “randomised controlled trial” in the title, abstract or keywords. Notably, by 2023, the number of research outputs had more than doubled compared to 2014.

One key issue is the highly individualised nature of Chinese Medicine regimens. Each patient’s management is tailored to their specific condition, making it difficult to standardise the interventions across a study population, a typical requirement for classical RCTs. Besides, the traditional multidimensional symptom-based diagnostic and disease classification system used in Chinese Medicine based on the assessment of pulse, tongue, and other symptoms are not perfectly aligned with Western medicine, complicating the selection of participants for RCTs in Chinese Medicine.

Furthermore, blinding, an effective method commonly used in RCTs to minimise different types of bias, is often difficult in Chinese Medicine studies, especially for acupuncture, cupping and herbal treatments.^[1] Designing a placebo control that closely mimics Chinese Medicine treatment but being inert is challenging. Last but not least, the RCTs of Chinese Medicine were often investigator-initiated with limited resources, leading to short follow-up periods and limited sample size, which may not be sufficient to demonstrate the long-term benefit of Chinese Medicine.

In recent years, advancements in RCT design have been introduced in response to these challenges. Several Chinese Medicine RCTs have been published in internationally renowned journals, highlighting their scientific rigour and clinical significance in contemporary medical research.

A multi-centre pragmatic RCT^[2] successfully integrated the Chinese Medicine symptom-based pattern differentiation into the RCT design by using stratified randomisation. The trial assessed the protocolised Chinese Medicine service and demonstrated a significant effect of Chinese Medicine service in stabilising the glomerular filtration rate in patients with diabetic kidney disease. Another double-blind RCT^[3] enrolled 3,110 patients from 133 hospitals and demonstrated that a Chinese traditional medicine, Qiliqiangxin Capsule, significantly reduced hospitalisation for heart failure and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF) when added to standard therapy. Another RCT^[4] found that the Chinese Medicine compound Tongxinluo Capsule, when added to guideline-directed therapies for patients with acute ST-segment elevation myocardial infarction (STEMI), significantly improved 30-day and 1-year clinical outcomes, including reductions in major adverse cardiac and cerebrovascular events and cardiac death.

A recent study^[5] published in The Lancet has sparked unprecedented interest in this area. The Chinese Herbal Medicine in Patients with Acute Intracerebral Haemorrhage (CHAIN) trial aimed to evaluate the efficacy and safety of the Chinese Medicine herbal compound FYTF-919 for treating intracerebral haemorrhage. This multicentre RCT enrolled 1,648 patients with acute moderate to severe spontaneous intracerebral haemorrhage. The trial found no overall significant effect of FYTF-919 on functional recovery, survival, or health-related quality of life overall. Nevertheless, unlike a previous trial^[6] in which traditional Chinese Medicine with properties of promoting blood circulation and removing blood stasis increased the risk of bleeding after intracerebral haemorrhage, the CHAIN trial demonstrated the safety of FYTF-919 in patients with acute intracerebral haemorrhage.

In the era of evidence-based and precision medicine, high-quality RCTs enhance the scientific rigour of Chinese Medicine and produce scientific evidence that supports clinical decision-making. This improves communication and integration with the general medical community. Advancement in trial design is necessary to bridge the epistemology of Chinese Medicine and Western medicine. Emerging large-scale RCTs are generating evidence of the effectiveness of Chinese Medicine in treating various diseases, filling a gap that has persisted for decades.

The evidence also supports healthcare policies and regulations and will drive further funding and investment into Chinese Medicine research and practice. Moreover, deeper analysis of the effectiveness of real-world Chinese Medicine practice through population-based pragmatic RCTs will help identify new products and services or new indications for existing regimens, such as standard Chinese Medicine formulations and evidence-based Chinese Medicine therapies, fostering economic growth within the pharmaceutical and healthcare sectors.

^[1] Chan, Kam Wa, et al. “Design of Clinical Trials in Integrative Medicine: The Issue of Personalization.” European Journal of Integrative Medicine, vol. 68, Elsevier BV, Apr. 2024, pp. 102365–65, https://doi.org/10.1016/j.eujim.2024.102365.

^[2] Chan, Kam Wa, et al. “Add-on Rehmannia-6–Based Chinese Medicine in Type 2 Diabetes and CKD.” Clinical Journal of the American Society of Nephrology, vol. 18, no. 9, Lippincott Williams & Wilkins, June 2023, pp. 1163–74, https://doi.org/10.2215/cjn.0000000000000199.

[3] Cheang, Iokfai, et al. “The Traditional Chinese Medicine Qiliqiangxin in Heart Failure with Reduced Ejection Fraction: A Randomized, Double-Blind, Placebo-Controlled Trial.” Nature Medicine, vol. 30, no. 8, Nature Portfolio, Aug. 2024, pp. 2295–302, https://doi.org/10.1038/s41591-024-03169-2.

[4] Yang, Yuejin, et al. “Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients with Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.” JAMA, vol. 330, no. 16, Oct. 2023, pp. 1534–45, https://doi.org/10.1001/jama.2023.19524.

[5] Guo, Jianwen, et al. “Traditional Chinese Medicine FYTF-919 (Zhongfeng Xingnao Oral Prescription) for the Treatment of Acute Intracerebral Haemorrhage: A Multicentre, Randomised, Placebo-Controlled, Double-Blind, Clinical Trial.” The Lancet, Dec. 2024, pp. S0140-6736(24)02261X, https://doi.org/10.1016/S0140-6736(24)02261-X.

[6] Zeng, Liling, et al. “Safety and Efficacy of Herbal Medicine for Acute Intracerebral Hemorrhage (CRRICH): A Multicentre Randomised Controlled Trial.” BMJ Open, vol. 9, no. 5, BMJ, May 2019, p. e024932, https://doi.org/10.1136/bmjopen-2018-024932.