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Global Translational Medicine Evidence-based approach for TCM development

holistic nature of treatments may make it more challenging in combination with RWD and RWE to support regulatory
to demonstrate effectiveness using conventional methods. submissions. Although initially proposed for rare disease
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drug development, this innovative approach can also
5.2. Composite hypothesis for safety and efficacy be applied to TCM development, particularly when the
As discussed in Section 3, the Western approach – powering sample size required to demonstrate safety is not feasible
the intended clinical trial based on efficacy endpoint alone within the intended RCT. It should be noted that the use
– for evaluating the safety and efficacy of WMs under of RWD/RWE in support of TCM regulatory submissions
development may not be appropriate regardless of whether is scientifically valid only under the assumption that RWD
WMs target specific organs. Unlike WMs, it is suggested is representative of the target patient population under
that the modernization of TCM, which focuses on global study. Thus, a pre-study evaluation of the RWD in terms of
dynamic balance/harmony among organs, should consider its representativeness, bias, consistency, data quality, and
testing composite hypotheses of safety and efficacy at the relevance is strongly recommended.
same time. However, this approach often requires a larger
sample size to achieve statistical significance and detect 5.4. TCM clinical trial design
clinically meaningful differences or safety concerns. To Designing clinical trials for TCM that accurately reflect its
address this challenge, an innovative approach based on unique diagnostic and therapeutic approaches is essential
probability statements can be employed for sample size for integrating TCM into global health-care practices.
justification. A well-fitted clinical trial design for TCM, such as the
For example, in a TCM clinical trial, the composite one described by Fu and Chow, offers a comprehensive
hypotheses could be set up as follows: structure that bridges the methodologies of WM and
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(i) Null hypothesis: The TCM is ineffective and unsafe TCM.
(ii) Alternative hypothesis: The TCM is not ineffective In this design, subjects are initially randomized
and not unsafe. into two groups. One group undergoes screening using

By testing these hypotheses with a reasonable number established Western study endpoints, while the other
of subjects, researchers can assess the safety and efficacy is screened through Chinese diagnostic procedures.
of the TCM under investigation. If the null hypothesis Following screening, eligible participants in each group
is rejected, it indicates that there is insufficient evidence are further randomized to receive either a test treatment
to conclude that the treatment is “not unsafe” and “not (T) or a control (C). This secondary stratification creates
ineffective.” four distinct subgroups, each receiving an evaluation
either in the Western manner or according to Chinese
This approach allows a more comprehensive evaluation methods. Figure 2 provides a visual illustration of the
of TCM treatments by considering both safety and efficacy design.
aspects. Using composite hypotheses allows researchers to
better align their statistical methods with the holistic nature The primary advantage of this design is its ability to
of TCM, which emphasizes the importance of balance and provide a robust comparative analysis of TCM and WM
harmony within the body. In addition, this approach can treatment effects within the same study framework. By
streamline the clinical trial process for TCM treatments by evaluating the treatment effects using both Western and
enabling the concurrent assessment of safety and efficacy, Chinese diagnostic and evaluation methods, the study
potentially reducing the need for separate trials. design allows for a nuanced understanding of how TCM
treatments perform under different evaluative lenses. This
5.3. The use of real-world design/RWE in support of dual approach facilitates a more comprehensive evaluation
regulatory submission of TCM’s efficacy, potentially uncovering benefits or effects

Expanding on the concept introduced in the previous that might be overlooked if only traditional Western
section, Chow suggested a novel two-step approach for methodologies were employed.
evaluating the efficacy of a test drug. The first step involves Furthermore, this design enables the examination of
testing for “not-ineffectiveness” (N), followed by testing for the consistency between Western and Chinese evaluation
effectiveness (S) once the not-ineffectiveness of the test drug methods across the subgroups. Such an analysis can
has been established. This approach is applicable when reveal how TCM treatments’ efficacy might be perceived
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the probability of inconclusiveness has little or no clinical differently through the paradigms of Western and Chinese
significance and can be considered negligible. To rule medicine, offering insights into the comparative validity
out the probability of inconclusiveness, Chow proposed and reliability of outcome measures across these medical
utilizing data from the intended randomized clinical trial systems.

Volume 3 Issue 3 (2024) 6 doi: 10.36922/gtm.4190