On November 21, 2014, the China Food and Drug Administration (CFDA) published a draft guideline on multi-regional clinical trials (MRCT) (the “MRCT Guideline”), soliciting public comments by December 10, 2014.
CFDA acknowledged in the draft MRCT Guideline that data generated from MRCTs in China could be used to support the registration of the underlying drugs in China, to the extent the MRCT is conducted in compliance with CFDA regulations. Sponsors are encouraged to conduct MRCTs in China for serious diseases and those therapeutic areas with unmet clinical needs. Sponsors are also encouraged to conduct pivotal studies in China and regional studies targeted to the Chinese patient population.
When seeking CFDA approval to conduct an MRCT in China, sponsors should submit the same regulatory dossier as they would submit to regulatory agencies in developed countries, including complete clinical protocol and supporting data, and the application should meet the requirements defined in the CFDA’s Drug Registration Regulation. To use data generated from an MRCT to support future drug registration in China, at least two countries (including China) would be included in an MRCT.
In order to use MRCT data to support a drug registration in China, sponsors should, in particular, (i) conduct an overall assessment on the global trial data, followed by a trend analysis on trial data generated from Asian and Chinese patients; (ii) consider whether patients enrolled in China are representative of the overall patient population in China; and (iii) ascertain whether the number of Chinese patients is statistically sufficient to conclude that the drug is safe and effective for Chinese patients. Furthermore, all study sites in and outside China must be available for on-site inspection by CFDA.
Changes to the MRCT protocol post-CFDA’s approval require sponsor reports to CFDA and to ethics committees if they relate to the study purpose or may significantly impact safety or study quality.
The draft MRCT Guideline provides some high-level points to consider in designing an MRCT, including disease epidemiology, medical practice, drug metabolism, dose selection, efficacy endpoint, sample size and statistical analyses, as well as inclusion of a Data Safety Monitoring Board, an independent endpoint adjudication committee and a central laboratory.
While the draft MRCT Guideline attempts to provide more detailed technical requirements in designing and implementing MRCTs in China, it fails to address one highly-debated issue: how an MRCT-based drug registration in China will be procedurally treated in contrast to a regular import drug registration.