ICH E17 Guideline some ICH regions. The justification (including safety considerations) for the use of an unapproved drug should therefore be described in the protocol based on scientific infor- mation, treatment guidelines and other relevant documents. Development status (e.g. no plan for development, under development, under regulatory review) of the unapproved drug in the region should also be described in the protocol. Plans for post-study treatment, including continued access to unapproved comparator, should be considered and provided to the patient in the informed consent.
2.2.9 Handling Concomitant Medications In general, drugs used concomitantly with the investigational drug should be the same throughout the regions to the extent possible, but there may be some differences in the drugs and/or doses actually used due to variations in medical practices. This could be acceptable if not expected to substantially impact trial results. The clinical trial protocol should specify allowable and not allowable concomitant medications and doses. Concomitant medications may be required in the protocol as an important part of the treatment.
In circumstances where approved drugs are combined with an investigational drug (e.g., a combination regimen of anticancer drugs) the same dosage regimen in all regions should generally be applied. If required by protocol, concomitant medications that are not approved in a region should have their use justified based on scientific infor- mation, treatment guidelines and other relevant documents. This could include documen- tation that the concomitant medication is approved in at least one of the ICH regions.
It should generally be allowed to use an unapproved concomitant medication, however the impact of using the unapproved concomitant medication in the relevant regions should be discussed with regulatory authorities and described in the protocol. The medication will need to be supplied in regions in which it is otherwise not available, only available at different strength and/or dosage form, or if a region cannot secure continuous supply dur- ing the course of the trial.
Regional differences in the use and dosing of concomitant medications that may have impact on drug responses should be considered in advance and these medications includ- ing changes in doses should be documented during the trial. The previous considerations may also be applicable to concomitant therapy other than medications (e.g., compression stockings in the post-operative setting, medical devices). 25