Master Protocols are complex innovative designs that offer tangible benefits to both sponsors and patients including increased patient centricity, and efficiency in drug development. Randomisation, with Adaptive Design Features, is an essential study design element of Master Protocols that contributes towards patient centricity. However, for the patient centric benefits to be realised, the Randomisation System must be implemented appropriately with the necessary flexibility. This paper will focus on how the Randomisation design and system implementation of Master Protocols can effectively achieve patient centricity.
Master Protocols (e.g., Basket, Umbrella, and Platform trial designs) are complex innovative designs that offer tangible benefits to both sponsors and patients. The FDA defines a Master Protocol as “a protocol designed with multiple sub-studies, which may have different objectives and involve coordinated efforts to evaluate one or more medical products in one or more diseases or conditions within the overall study structure.” Compared with conducting a traditional stand-alone trial, Master Protocols offer several benefits such as increased flexibility and efficiency in drug development, the ability to share control arms/reduced sample sizes, shared infrastructure, increased data quality and patient centricity. Therefore, Master Protocols have the potential to identify treatments that are effective or ineffective quicker than traditional trials.
The growing enthusiasm of Master Protocols is attributed to recent successful trials within various therapeutic areas such as COVID-19, glioblastoma, oncology, and amyotrophic lateral sclerosis. Master Protocols are efficacious within both small scale and larger scale patient populations. In relatively small patient populations, Master Protocols are able to efficiently and effectively test multiple targeted agents/therapeutic strategies. For instance, Master Protocols have the ability to provide optimal therapy customisation to individuals with specific biomarkers, as demonstrated by successful FDA indication approvals of biomarker-targeted Master Protocol trials. Regarding the larger scale, the FDA indicates that the efficiencies within the Master Protocol framework are particularly beneficial during public health emergency settings such as COVID-19 when there is a need to find effective therapies at a rapid pace. Across the COVID-19 health emergency, numerous traditional trials yielded no significant findings, whereas several Master Protocols (e.g., NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) studies), continue to produce reliable evidence for investigational therapies. Further, the FDA expects that Master Protocols will continue to play an important role within COVID-19, as well as any potential future pandemics.
Whether it be on the larger or smaller scale, the Master Protocol framework is well-suited to deliver efficient patient-centred clinical trials. As such, since Master Protocols have the ability to adapt by design, this enables continuous learning and has significant advantages for patients. In particular, two major hallmarks of innovation of Master Protocols are study design (i.e., Randomisation with Adaptive Features) and infrastructure (Randomisation Processes). This paper will describe the Adaptive Design Features related to Randomisation and how they are applied to Master Protocols, their implementation within the Randomisation System, and how these components can achieve patient centric benefits.
