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.

The source of clinical evidence in drug development has been limited to be generated from clinical trials for many years. However, the evidence generation should be extended to Real World Data (RWD), which will play a key role anywhere. The ICH GCP renovation recommends selecting from a variety of clinical trial designs and data sources choices where innovative new drugs will be provided to patients as an earlier approval of the new drug application. In the early-stage approval system of the Ministry of Health of Labor and Welfare and the revision of GPSP in Japan, it is clearly stated that medical databases and patients' registry will be available. In this manuscript, we summarize the following cases of the utilizing RWD in drug development； (1) submitting data for a new drug application, (2) planning of clinical trials and patients' recruitment for clinical trials, (3) collecting clinical trial data using Electronic Health Record as data source, (4) assessing clinical outcomes and diagnosis, (5) developing strategies of drug development, drug pricing and access. Although there are many challenges in each application and the improvement in the infrastructure and regulatory environment is desired, we hope the progress of RWD use in the practice of drug development without waiting for that.

Good Post-Marketing Study Practice (GPSP) changed in April 2018, allows pharmaceutical companies to use a real-world data for pharmacovigilance activity. On the other hand, it is known that there are 3 major dimensions of pharmacovigilance： “Monitoring, vigilance, and science：building the best evidence” ,“Regulation, industry, and legal system：ensuring public health” and “Medicine, medicines, and uncertainty : doing good to patients” . Therefore, in this article, we consider how the change of GPSP reflects on the 3 features of pharmacovigilance.

In general, it is thought that the change of GPSP contributes pharmacovigilance, considering the 3 features of pharmacovigilance. On the other hand, there are some points to improve pharmacovigilance system：1) how a safety question for pharmacovigilance should be addressed, 2) how information of routine pharmacovigilance should contribute to a safety question to be addressed, 3) how a feasibility assessment (assessment of data source before conducting a formal comparative activity) should be conducted, and 4) a necessity of a variety of methodology and data sources such as descriptive studies and disease registry. These improvements will contribute to global standardization and give us global competence.

Overall, it is very difficult to consider the best safety question, data source and methodology from many options. However, it is thought that keep considering them in order to accumulate experiences is important for our ultimate goal, which is to help our patients. We expect more discussions among all the stakeholders together.