OBJECTIVES

Novel trial designs have been introduced in drug development. The study aims to investigate the interactions with regulators in the United States (US) and Japan on innovative trial designs.

METHODS

A comprehensive literature review was conducted of the Food and Drug Administration (FDA) and Pharmaceuticals and Medical Devices Agency (PMDA) websites about the innovative trial designs, in PubMed® database and in grey literature

RESULTS

Both regulators have established initiatives to expedite new drug development, facilitating faster patient access to innovation.

Via the breakthrough therapy designation started in 2012 in the US, the FDA provides close consultations on an efficient drug development program, including guidance on alternative trial designs and smaller clinical trials, beginning as early as Phase 1. The designation is granted for a new therapy, which may indicate substantial clinical advantages over the exsiting medications.

In 2018, the FDA started the five-year Complex Innovative Trial Design (CID) Pilot Meeting Program to support the use of a highly innovative clinical trial design, across different therapeutic areas. The meetings with the FDA provide regulatory input on the CID in late-phase drug development. The draft guidance on master protocol for cancer drugs and the guidance on adaptive trial designs reflect the data generation in clinical trials with novel designs.

In 2015, the SAKIGAKE designation was established in Japan. Through this designation the regulator works closely with the applicant during the product lifecycle, including support in late-phase clinical trials with innovative designs. The designation is granted for an innovative drug intended to treat serious illnesses or if an improved efficacy over the available treatment is expected.

CONCLUSIONS

Both regulators grant intensive individual communications with sponsors focusing on innovative trial designs. As no global accepted regulatory standards for innovative clinical trials exist, separate contact with each regulator is recommended.