The loss of exclusivity from several drug therapies largely used bring new attention the issues of safety, efficacy and following the switch from one drug to another (i.e., biosimilar and/or generics) with the same indication. This is not a problem that can be related to regulatory or economical factors. The increase of patients exposed to chronic conditions and the introductions or more pharmaceutical alternatives with same therapeutic indications yield for studies able to verify the effectiveness and safety even when switch from more drugs is considered by practitioners. Recent multiregional studies showed that the switch from phenomenon is not a rare event, especially with biologic drugs, frequent even before the introduction of biosimilar not only because of economical reasons. For instance, a study made in our region (Lazio) showed that around 17% of patients treated with epoetins have been exposed to same kind of switch between drugs with same therapeutic indications. In this context it became crucial to explore new methodologies in order to verify before and after drug registrations how the potential switching affect final health outcomes. Limitations and design of the new studies need to be critically analysed.