On Friday, September 9th, the FDA announced the availability of a draft guidance entitled “E17 General Principles for Planning and Design of Multi-Regional Clinical Trials.” The draft guidance, which was developed by the International Council for Harmonisation (ICH), was issued in June of this year and is intended to help sponsors with the planning and design of multi-regional clinical trials (MRCTs), as well as facilitate more efficient drug development and provide earlier access to medicines.
The recommendations included in the draft guidance apply mainly to drugs and biological products, but could also be applied to studies involving other types of treatments. Furthermore, the document states that its primary focus is “on MRCTs designed to provide data that will be submitted to multiple regulatory authorities for drug approval (including approval of additional indications, new formulations and new dosing regimens) and for studies conducted to satisfy post-marketing requirements.”
According to the draft guidance, an MRCT is “a clinical trial conducted in more than one region under a single protocol.” Typically, MRCTs are the preferred option when sponsors are planning to submit a drug to various regulatory agencies in multiple regions. “The underlying assumption of the conduct of MRCTs is that the treatment effect is clinically meaningful and relevant to all regions being studied.”
Value of MRCTs
In the past, many drug development programs were focused on specific regulatory regions, only making use of MRCTs when either the disease or condition was rare or when very large numbers of subjects were required. However, recently we have seen an increase in the number of global regulatory strategies being used. The reason for this shift? Although more planning and coordination is involved, MRCTs and global regulatory strategies increase trial efficiency and help to facilitate more rapid drug development and availability. In addition, MRCTs provide sponsors with the following benefits:
- “Allow for an examination of the applicability of a treatment to a diverse population.”
- “Facilitate simultaneous global drug development by reducing the number of clinical trials that need to be conducted separately in each region, thereby avoiding the ethical issue of unnecessary duplication.”
- Ability to simultaneously submit marketing authorization applications to multiple regulatory agencies in different regions.
Basic Requirements & Key Considerations
The draft guidance provides a number of requirements and considerations that should be considered by sponsors when conducting MRTCs. These include, but are not limited to:
- “Participating regions should share a unified trial hypothesis with common comparators, and a primary endpoint which is considered clinically meaningful in all regions.”
- “Participating sites should be able to enroll a well-described, well-characterised population of eligible subjects.”
- All participating sites are required to meeting applicable quality and regulatory standards.
- “Specifically, MRCTs should be conducted in compliance with ICH E6-GCP standards in all regions and sites, including making sites available for GCP inspections by relevant regulatory authorities.”
- “Monitoring plans and other quality checks should be pre-specified and implemented in order to address potential risks to trial integrity.”
- “Timely and accurate flow of information should occur between the sponsor, trial management team and participating sites.”
- All investigators and study personnel in all regions should complete a common training program before initiating the trial.
- This will help ensure that the trial objectives are met through a standardized implementation of the trial protocol, and that an appropriate level of data quality is achieved.
Interested in learning more about FDA’s draft guidance? Stay tuned… Part two is coming soon with details on clinical trial design and protocol-related issues.