RCTs for Chinese Traditional Medicine and Botanical Drug Development

In the latest issue of JAMA (Journal of American Medical Association), Yang et al published a paper "Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction The CTS-AMI Randomized Clinical Trial". The CTS-AMI randomized clinical trial is one of the first times that a traditional Chinese medicine has been tested in a large-scale, Western-style clinical trial.

Historically, the efficacy and safety of Chinese Traditional Medicine are not based on randomized, controlled clinical trials and,  therefore, questioned by many. In the era of evidence-based medicine, researchers in China started to adopt and conduct the RCTs for Chinese Traditional Medicine. These RCTs were published primarily in journals in Chinese. It is rare for the CTS-AMI RCT study to be published in the prominent English journal, JAMA. 

In an article "Traditional Chinese Medicine Proves Effective in Modern Clinical Trial", Dr Matthew Saybolt, a cardiologist with the Hackensack Meridian Jersey Shore University Medical Center commented on the study 

"I am not aware of any other large, well-run trials like this studying traditional Chinese medicine. This is a rarely run type of study, and I congratulate the authors for their work and publication in such a prestigious medical journal. The study was well conducted with a large sample size that was well powered to measure the outcomes.

In this trial, there is clearly a benefit to patients treated with this Chinese medicine compound compared to placebo

A reduction in death, reinfarction or complications after a STEMI is a very exciting finding. We have for some time been trying to bend the curve and improve mortality and complications after STEMI. Any new therapy, if safe, that can accomplish this would be very appealing to patients and physicians alike."

Saybolt said he also observed some weaknesses in the way the study was conducted, one of which was that the participants were entirely Chinese citizens and predominantly male.

"Thus the findings may not be generalizable throughout the world or to women," he said. "Furthermore, the patients were less frequently—compared to the United States, for example—treated with traditional proven medicine after their myocardial infarctions. Therefore, the effect of the Chinese medicine may have been augmented by the lack of patient exposure to proven therapies.

"However, there was equivalent low utilization of these traditional medications in both groups," he continued. "Furthermore, the study drug Chinese medicine compound was composed of multiple plant and insect products. Thus, we do not know which component or combination of components were the active ingredients and what is the correct dose."

If Chinese Traditional Medicine Compound needs to be approved in the US or other countries, the RCTs need to be conducted in multi-national clinical trials with a broad patient population. Given that the Chinese traditional medicine Compound is extracted from herbals, the drug development program will need to follow regulatory guidance such as USFDA guidance for the industry "Botanical Drug Development". 

Recent years, psilocybin, the primary psychoactive substance in 'magic mushrooms' has been tested in clinical trials to study its effect on major depression disorder, PTSD,... the drug development process for psilocybin (if extracted from magic mushroom) will need to follow the FDA guidance ""Botanical Drug Development"" and "Psychedelic Drugs: Considerations for Clinical Investigations ".