Recently, the increasing risk of drug development has impelled pharmaceutical enterprises to improve ways of research and exploitation. Adaptive design has been proposed for decades. Although the theory of this design is not perfect, it has been recognized and applied worldwide as a decreasing risk of drug development to a certain extent. The traditional fixed design in western medicine isn’t entirely suitable for traditional Chinese medicine (TCM), while the adaptive design with integrity and variability features provides a new idea for TCM development. Hereby the application of adaptive design in TCM is regarded as an important procedure for promoting TCM modernization, and it has a wide prospective.
Due to the competition of new drug research and clinical requirement, speeding up drug development and marketing requires faster and more flexible clinical trial design that meets the ethical requirements. Different adaptive designs have emerged in clinical trials of different stages and purposes, for trial efficiency improvement. Adaptive design is more widely used in the field of oncology. Compared with traditional design, adaptive design is more complicated and requires higher level of methodology from researchers. Therefore, implementing adaptive design requires careful consideration and adequate preparation. This paper aims to summarize the design of adaptive methods used in different trial stages so as to provide reference for clinical research designers and implementers.
Randomization was the basis for the design and conduct of clinical trials. However, the traditional randomized controlled trials (RCTs) were often randomized in a fixed manner with unbalanced potential covariates, which spured researchers to develop a more flexible and practical randomization method. Thus, the adaptive randomization emerged as the time needed. In this paper, the application of adaptive randomization in clinical trials was introduced, and its key points of implementation, advantages and disadvantages were summarized. The development space of the adaptive randomization in clinical applications was also discussed, and it provided evidence for the development of the drug clinical trials in China.
Master protocol with adaptive design is a new complex innovative trial design that combines an adaptive treatment strategy and master protocol. It is more flexible and adjustable. In the complex clinical trial environment, the dynamics emphasized in this design are consistent with the idea of traditional Chinese medicine (TCM) syndrome differentiation and treatment. In this study, we summarized its concept, characteristics and advantages, and we also discussed its application in TCM clinical research. We hope this paper can provide more thinking and suggestions for TCM clinical trials.
The modern clinical research evaluation system has been increasingly emphasizing the evaluation of individual patients' clinical characteristics, diagnosis and treatment plans, and complex intervention measures. Traditional randomized controlled trial evaluated fixed interventions and non-adaptive treatment plans, which cannot meet the needs of evaluating adaptive interventions. This made researchers more inclined to explore an individualized and adaptive clinical trial design, then sequential multiple assignment randomized trial (SMART) emerged as the time needed. This article introduces the principles, key elements, and implementation points of SMART design, further explores the limitations of the mismatch between traditional Chinese medicine clinical trial design and syndrome differentiation treatment, and proposes that SMART design can meet the needs of traditional Chinese medicine clinical trials to inspire researchers in designing their plans.