Impact of Different Regulatory Requirements for Trial Endpoints in Multiregional Clinical Trials

Regulatory agencies in different parts of the world may have different requirements for endpoints, which significantly affects the design and conduct of registrational multiregional clinical trials (MRCT). In particular, different health authorities may request or require different endpoints as primary or key secondary hypotheses in phase 3 MRCTs. In addition, differences between regions may involve the time point considered primary, patient populations analyzed, study design, or noninferiority margins. No guidance exists on how pharmaceutical companies should handle such regional differences, and harmonized guidance across regions would be useful. Initial steps in any global program should involve attempts to reach consistency in an MRCT. We review scenarios involving different health authority requirements for endpoints and other study design features and recommend approaches to handling differing health authority requirements within a global program, when a consistent global approach is not acceptable to all regulatory authorities.