ICH E17 Guideline The choice of comparators should be justified in the study protocol based on sci- entific and other relevant information, including international treatment guide- lines. Active controls should in principle be dosed and administered in the same way in all regions. If the approved dosing regimen of active comparators are different among regions, the proposed study dosing regimen should be justified by availa- ble data, and the justification should be included in the study protocol. Addition- ally, the impact of such a dosage difference on analysis and evaluation of MRCT data should be considered in the planning stage.
The same dosage form (e.g., liquid drugs vs tablets) for active comparators should generally be used among regions participating in MRCTs to ensure consistency of treatment effects and data interpretability. Different dosage forms could be used if the dissolution profiles and bioavailability are well-characterised, and dif- ferences are negligible. In order to ensure the consistent quality of the active comparators, it is recom- mended to use the same source in all participating regions.
When active compar- ators from different sources are used in MRCTs, justification should be provided (e.g., in form of Certification of Analysis or report from the manufacturer on equivalence or dissolution studies), to ensure that the comparator has the same quality in all participating regions. The most comprehensive product information used in a region is recommended to be used consistently in all participating regions. If the product information differs from local product information (e.g., differences in the warnings, adverse reac- tions), this should be explained in the local informed consent form.
If different drugs in the same or similar drug class are proposed to be used as active comparators, justification should be provided in the protocol based on available scientific evidence. The above considerations may also be applicable in case of comparators which are se- lected based on investigator's choice of local standard care. Active comparators in MRCTs should ideally be approved in all participating regions. However, there could be situations where active comparators used in MRCTs are not approved or not available in specific regions, but have been approved and available in 24