RESUMEN
Pharmaceutical regulatory schemes concerned with real world data have been changing remarkably in terms of both drug development and post-marketing.As for drug development, ICH proposed “GCP Renovation” , which includes modernization of E8 Guideline (General Consideration for Clinical Trials) and subsequent renovation of E6 Guideline (Good Clinical Practice). It covers pragmatic clinical trials, randomized controlled trials using patient registry data, and even observational studies using real world data. In the US, “The 21st Century Cures Act” refers to the proposal concerning speeding up the approval review by making clinical trials more efficient. In fact, there are some cases where real world data was used in the approval review of expanding the application. Also, in Japan, Clinical Innovation Network (CIN) plan was announced, and utilizing the natural history data like patient registry as the control group of clinical trials for the approval review is now under consideration.As regards post-marketing surveillance, “Conditional & Accelerated Approval” (October 20, 2017, Yakuseiyakushinhatsu 1020 No. 1) stated that post-marketing confirmation of validity of efficacy and safety using real world data, such as Medical Information Database Network (MID-NET) project and patients registries in CIN plan, is required to get the early approval. Moreover, “The Ordinance on Good Post-Marketing Practice” (October 26, 2017, MHLW Ordinance No. 116) newly provided “Post-marketing Database Study” , which is conducted by use of medical information database like MID-NET, and utilizing real world data for post-marketing safety monitoring began.
RESUMEN
For regulatory approval of a new drug, the most preferred and reliable source of evidence would be randomized controlled trials (RCT). However, a great number of drugs, being developed as well as already marketed and being used, usually lack proper indications for children. It is imperative to develop properly evaluated drugs for children. And expanding the use of already approved drugs for other indications will benefit patients and the society. Nevertheless, to get an approval for expansion of indications, most often with off-label experiences, for drugs that have been approved or for the development of pediatric indications, either during or after completing the main drug development, conducting RCTs may not be the only, if not right, way to take. Extrapolation strategies and modelling & simulation for pediatric drug development are paving the road to the better approval scheme. Making the use of data sources other than RCT such as EHR and claims data in ways that improve the efficiency and validity of the results (e.g., randomized pragmatic trial and randomized registry trial) has been the topic of great interest all around the world. Regulatory authorities should adopt new methodologies for regulatory approval processes to adapt to the changes brought by increasing availability of big and real world data utilizing new tools of technological advancement.