International regulatory frameworks for hybrid modern clinical trial designs

Adaptive designs, Bayesian methods, master protocols, decentralized clinical trials (DCTs) and real-world evidence (RWE) are all examples of novel and more innovative clinical trial designs that are increasingly being utilized to make drug development more efficient, flexible and patient-centred. This review examined regulatory guidance from the FDA, EMA and ICH to determine what they think and expect now and how they intend to utilize these new trial approaches.

The results show that all three regulatory bodies agree with adaptive designs, if they include predetermined rules, reduce Type I errors, and are validated through simulations. Bayesian methods are applied in some instances, such as when defining a rare disease, where it is necessary to define the prior and test the model.

Master protocols are highly efficient in practice, particularly in cancer and pandemic environments. However, only the FDA and EMA have comprehensive guidance frameworks in place.

Rajesh Kumar Gajendran
Principal Data Scientist,
Navitas Life Sciences,
Tamil Nadu, India

Saravanan Govindaraj
Principal Data Scientist,
Navitas Life Sciences,
Tamil Nadu, India

Venkatesan Balu
Director - Global Data Sciences,
Navitas Life Sciences,
Tamil Nadu, India

Published by Pharma Innovation Journal, March 2026

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