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Global Translational Medicine Evidence-based approach for TCM development

such as clinical, surrogate, or biomarker endpoints in terms 5. Innovative thinking on the
of sensitivity and specificity of the developed instruments. modernization of TCM development
The validated instrument should be able to inform the
disease status and/or treatment effect at various stages or In the pursuit of modernizing TCM development,
phases of clinical development/investigation. several innovative approaches from other fields can be
adapted to enhance TCM clinical trials. These approaches
4.4. Examples of current TCM modernization efforts include: (i) demonstrating “not unsafe” for safety and “not
Recent efforts to modernize TCM have resulted in ineffectiveness” for efficacy; (ii) using composite hypotheses
significant advancements that bridge traditional practices to evaluate both safety and efficacy simultaneously; and
with modern scientific approaches. One notable example is (iii) incorporating RWD and RWE to support regulatory
the clinical research on carotid artery plaque intervention approval. These innovative approaches will be briefly
with the Tongxinluo capsule. This multicenter, described below.
randomized, double-blind, placebo-controlled study, 5.1. The concept of demonstrating not unsafe and
led by Zhang et al., involved 1212 patients with not ineffectiveness
17
carotid atherosclerotic plaque. The study demonstrated
that Tongxinluo therapy, when added to conventional The concept of demonstrating “not unsafe” and “not
treatment, could slow the progression of carotid intima- ineffectiveness” differs from the conventional approach
media thickness, plaque area, and vascular remodeling of demonstrating “safe” and “effective.” In this approach,
index, while also reducing cardiovascular events with a the null hypothesis of ineffectiveness is tested against
strong safety profile. the alternative hypothesis of “not ineffectiveness” rather
than “effectiveness”. Rejecting the null hypothesis in
21
Another example is the global success of artemisinin, a favor of “not ineffectiveness” does not necessarily imply
compound derived from the TCM herb Artemisia annua. effectiveness. This approach can be particularly useful in
18
Discovered by Tu Youyou, artemisinin has become a first- TCM development as well as in the development of drugs
line treatment for malaria, endorsed by the WHO. Its for rare diseases. 21
widespread use has contributed significantly to malaria In practice, researchers typically test the null hypothesis
control, including near eradication in regions such as at the α = 5% level of significance, although some prefer
the Comoros Islands, and earned Tu the Nobel Prize in testing at the α = 1% level. If the observed P-value
Physiology or Medicine in 2015. 19
falls between 1% and 5%, the test result is considered
In addition, galantamine, extracted from the TCM inconclusive. In placebo-controlled studies, “not
herb Lycoris radiata, is now an approved treatment for ineffectiveness” conceptually includes both the portion of
Alzheimer’s disease in Europe. As an acetylcholinesterase inconclusiveness and effectiveness (Figure 1).
inhibitor, galantamine’s success showcases the potential of Applying this approach to TCM clinical trials can
TCM-derived compounds in treating complex neurological provide a more nuanced understanding of the efficacy of
conditions. 20 TCM treatments. By demonstrating “not ineffectiveness,”
Despite the successes, it is essential to note that while researchers can show that a TCM treatment has the
compounds such as artemisinin and galantamine, derived potential to be effective, even if the evidence is not strong
from TCM herbs, have achieved global recognition and enough to claim definitive effectiveness. This approach can
widespread use; their development involved simplifying be particularly valuable in the context of TCM, where the
the complex formulations typical of TCM into single
compounds. These examples still reflect a degree
of Westernization, as the process of isolating active
compounds from TCM herbs tends to align more with
Western pharmaceutical practices than with traditional
TCM approaches. Therefore, while these examples
highlight the success of integrating TCM into modern
medicine, they also underscore the ongoing need for
TCM modernization that remains true to its holistic and
multi-component nature. The challenge lies in preserving
the complexity and synergy inherent in traditional
formulations while ensuring that they meet the rigorous Figure 1. The relationship between “effectiveness” and “not ineffectiveness”
standards of modern clinical practice. in placebo-controlled studies 21

Volume 3 Issue 3 (2024) 5 doi: 10.36922/gtm.4190