International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use has issued draft guidance titled E17 General Principles for planning and design of multi-regional clinical trials.
Indian clinical trial companies have welcomed the draft tripartite guidelines as it gives them a direction to conduct human studies in the international arena.
With the increasing globalisation of drug development, it has become important that data from multi-regional clinical trials (MRCTs) can be accepted by regulatory authorities across regions and countries as the primary source of evidence to support marketing approval of drugs.
The purpose of this guideline is to describe general principles for the planning and design of MRCTs with the aim of increasing the acceptability of MRCTs in global regulatory submissions. The guideline addresses some strategic programme issues as well as those issues that are specific to the planning and design of confirmatory MRCTs and should be used together with other ICH guidelines, including E2, E3, E4, E5, E6, E8, E9, E10 and E18.
Globalisation of drug development has increased the use of MRCTs for regulatory submissions in ICH regions as well as in non-ICH regions. Currently, it may be challenging both operationally and scientifically to conduct a drug development programme globally, in part due to distinct and sometimes conflicting requirements from regulatory authorities.
At the same time, regulatory authorities face increasing challenges in evaluating data from MRCTs for drug approval. Data from MRCTs are often submitted to multiple regulatory authorities without a previous harmonised regulatory view on the study plan. There are currently no ICH guidelines that deal with the planning and design of MRCTs, although the ICH E5 Guideline covers issues relating to the bridging of results from one region to another. The present guideline describes the principles for planning and design of MRCTs, in order to increase the acceptability of MRCTs by multiple regulatory authorities.
MRCTs are generally the preferred option for investigating a new drug for which regulatory submission is planned 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.
Ethnic factors are a major point of consideration when planning MRCTs. They should be identified during the planning stage, and information about them should also be collected and evaluated when conducting MRCTs. Participating sites should be able to enroll a well-described, well-characterised population of eligible subjects where differences between regions with respect to disease and population factors, medical practices are not expected to substantially impact safety and efficacy results.
The draft norms indicate that to harmonise subject selection, uniform classification and criteria for diagnosis of the disease should be implemented. When diagnostic tools like biochemical testing, genetic testing are needed for the selection of subjects, these need to be clearly specified. To ensure a subject’s condition is stable before starting the investigational drug, a prior observation period may be useful for control of some concomitant medications.