Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Mumbai, 400012, India.
Department of Pharmacology and Therapeutics, Seth GS Medical College & KEM Hospital, Mumbai, 400012, India.
Curr Rev Clin Exp Pharmacol. 2022;17(2):114-121. doi: 10.2174/1574884716666210316114157.
The concept of 'one size fits all' - one treatment for patients with a particular disease, seems to be outdated. The advent of precision medicine has prompted profound changes in clinical research and it allows researchers to predict more accurately, the prevention and treatment strategies for a specific disease population. Novel study designs are, therefore, essential to establish safe and effective personalized medicine. Basket, umbrella and platform trial designs (collectively referred to as master protocols) are biomarker enrichment designs that allow for testing more than one hypotheses within a protocol, thus accelerating drug development. These trial designs tailor intervention strategies based on patient's risk factor(s) that can help predict whether they will respond to a specific treatment. Basket trials evaluate therapy for various diseases that share a common molecular alteration, while umbrella trials evaluate multiple targeted therapies for a single disease that is stratified into subgroups based on different molecular alterations/ risk factors. These designs are complex and their major limitations stem from the fact that it would be inappropriate to completely replace histological typing with molecular profiling alone. However, in the upcoming decades, these trial designs are likely to gain popularity and improve the efficiency of clinical research. This article briefly overviews the characteristics of master protocol designs with examples of completed and ongoing clinical trials utilizing these study designs.
“一刀切”的理念——针对特定疾病的患者采用一种治疗方法，似乎已经过时。精准医学的出现促使临床研究发生了深刻的变化，它使研究人员能够更准确地预测特定疾病人群的预防和治疗策略。因此，新型研究设计对于建立安全有效的个体化医学至关重要。篮子、伞形和平台试验设计（统称为主方案）是基于生物标志物的富集设计，允许在一个方案中测试多个假设，从而加速药物开发。这些试验设计根据患者的风险因素（可帮助预测他们是否对特定治疗有反应）来定制干预策略。篮子试验评估针对具有共同分子改变的各种疾病的治疗方法，而伞形试验则根据不同的分子改变/风险因素将一种疾病分层为不同的亚组，评估多种针对单一疾病的靶向治疗方法。这些设计很复杂，其主要局限性在于，仅用分子谱图完全替代组织学分型是不合适的。然而，在未来几十年，这些试验设计可能会越来越受欢迎，并提高临床研究的效率。本文简要概述了主方案设计的特点，并举例说明了利用这些研究设计完成和正在进行的临床试验。
