适应性设计在临床研究中的优化及中医药研发应用

Optimization of Adaptive Design in Clinical Research and Inspiration for Traditional Chinese Medicine Research and Development

摘要:

近年来适应性设计逐渐在临床试验中崭露头角，得到了广泛的应用和拓展。相比于传统的随机对照试验，恰当的适应性设计在一定程度上能节约实验时间和资源，提高实验结果的有效性和论证强度，并且更符合伦理学要求，也有利于药物后续的上市研究。一方面，由于适应性设计更大的灵活性，控制Ⅰ类错误率、真正提高研究效力是其应用的难点。所以在研究中对适应性设计的规范应用和优化值得提前重点关注。如遵循良好的适应性设计原则，提前进行严格的方案预设计；科学应用贝叶斯动态模型、模拟方法等多种统计学方法及检查委员会等手段，以助于监测研究环节的科学性。另一方面，其灵活性恰好与中医药临床实际相契合。中医学的主要特点“整体观念”和“辨证论治”决定了中医临床提供的是一个动态的、个性化诊疗方案，而西药传统的固定研发方案限制了中医药“人用经验”的发挥。为解决中医药研发的这一瓶颈，创新性利用具有多重性和可变动性的适应性设计这一现代科学理论和方法可以为中医药临床研究与中药创新研发提供一个可行的新思路。通过学习美国食品药品监督管理局（FDA）批准上市的第一个口服植物药Crofelemer等新药案例的成功经验，探索适应性设计在临床研究方案中的更优解及在“三结合”中药审评体系中的角色和作用，进一步完善试验方案设计、明确试验方案要点，为中药复方临床药效、药理机制探索和上市后疗效评价开拓适应中医临床定位、体现作用特点和优势的创新研发应用方案。

Abstract:

In recent years， adaptive design has gradually emerged in clinical trials， gaining widespread application and expansion. Compared with traditional randomized controlled trials， appropriate adaptive design can save time and resources to some extent， improve the validity of the trial results and strength of the evidence， align better with ethical requirements， and facilitate subsequent drug market research. However， due to the greater flexibility of adaptive design， controlling type Ⅰ error rates and truly enhancing research efficiency are challenging aspects of its application. Therefore， the normative application and optimization of adaptive design in research deserve early focus， including adhering to good adaptive design principles， conducting rigorous pre-design planning， scientifically applying various statistical methods such as Bayesian dynamic models and simulation methods， and utilizing monitoring tools like monitoring committees to ensure the scientific integrity of the research process. Moreover， the flexibility of adaptive design aligns well with the practical realities of traditional Chinese medicine （TCM） clinical practice. The main characteristics of TCM， such as the holistic concept and treatment based on syndrome differentiation， determine that TCM provides a dynamic and personalized treatment plan. In contrast， the traditional fixed development approach of western medicine limits the application of "human experience" in TCM. To address this bottleneck in TCM research and development， the innovative use of adaptive design， a modern scientific theory and methodology with multiplicity and variability， offers a feasible new approach for TCM clinical research and the innovation of Chinese herbal medicine. By learning from successful cases such as the first Food and Drug Administration （FDA）-approved oral botanical drug， Crofelemer， researchers can explore optimal solutions for adaptive design in clinical research protocols and its role in the "three-combination" evaluation system for Chinese herbal medicines， further refine trial design， clarify key trial points， and develop innovative research and development applications that adapt to the clinical positioning of TCM and highlight the characteristics and advantages of TCM， paving the way for the clinical efficacy， pharmacological mechanism exploration， and post-market efficacy evaluation of Chinese herbal compounds.