Around the Globe

Nurturing Growth of RWD into RWE in Japan
Manami Yoshida
Shionogi & Co., Ltd.
Shinzo Hiroi
Shionogi & Co., Ltd.

eal world data (RWD) has grown into one of the buzzwords in the healthcare industry in Japan. Although utilizing sales data for pharmaceutical medicines in market surveys is an established practice based on RWD, changing circumstances and use of RWD in pharmaceutical and medical device companies in Japan have raised more issues and attention in recent years. The second DIA Health Economics Outcomes Research (HEOR) Workshop in Japan explored the ideal future direction for transforming RWD into real world evidence (RWE) suitable for regulatory decisions in the healthcare industry.

Key Takeaways

  • Glowing reviews of various applications for RWE offer hope, but unresolved issues remain. It is important to consider if the data are reliable enough to serve as evidence in a rationale for regulatory approval or disapproval of a future medical treatment.
  • Growing purposes for utilizing RWD in Japan include non-clinical research and pharmacovigilance.
  • Effective utilization of RWE is only half of the story; completing it will require continuous and collaborative discussion and actions by multifunctional stakeholders.
Current discussions of the ICH-GCP Renovation suggest that instructions for clinical trials using patient registries, pragmatic clinical trials, or other RWD will be included in its annex. Generating real world evidence (RWE) from real world data (RWD) requires specific expertise. To this end, many pharmaceutical and medical device companies are establishing new departments for RWE or for Health Economics and Outcomes Research (HEOR); even so, interactive understanding and collaboration across various functions or organizations is necessary for their success.

What Does GCP Renovation Mean?

Osamu Komiyama (Pfizer R&D Japan), a member of ICH E8 (R1) Expert Working Group, overviewed the forthcoming ICH GCP Renovation by focusing on quality control and other changes. Its scope has expanded beyond the traditional randomized clinical trial to include observational studies, both prospective or retrospective, as one potential source for generating RWE outside the conventional randomized clinical trial that could provide findings to health care practice or policy; and it will adapt the concept of “Quality by Design” to provide flexible yet appropriate guidance on the increasing diversity of clinical trial designs and clinical data sources.

Patient Registries and Databases

Patient registries initiated by academia provide an excellent example of introducing and promoting RWE in research because patient registries often enable research and development in a therapeutic area which has been neglected due to the infeasibility of conventional clinical trials. From the pharmaceutical industry perspective, hospital administrative databases have provided RWD for non-regulatory epidemiological or cost evaluation studies to maximize value of their products. At this moment, it is difficult to evaluate clinical outcomes or QOL using the data of hospital administrative databases. Not only hospital administrative databases but also the growth of other types of database and their industry use are desired. Here is one overview of medical big data in Japan. A program of registry-based infrastructure for efficient clinical development in Japan has also been initiated. Future growth of these data into evidence for regulatory purposes would make more efficient clinical development and lifecycle management possible.

Challenges for Regulatory Use

Many challenges for regulatory use of RWE are technical issues related to data systems and security, such as systems validation, security control, and protection of identifiable personal information. Another challenge is converting clinical information captured across various formats to CDISC data standards. While it is reasonable to use data from patient registries as external controls for clinical trials, it is important to consider the comparability of these two data sources, especially when evaluating efficacy. Randomized clinical trials reflecting real world clinical practice are still the best way to generate data for regulatory decisions.

In the closing panel discussion, Tomoko Ohsawa (Director, Office of Non-Clinical and Clinical Compliance) shared PMDA’s regulatory viewpoint on these and related topics. From the regulatory perspective, it is important to consider if RWD can be used as evidence supporting a rationale for future medical treatment: Were the data appropriately collected and managed with this regulatory intent?

PMDA remains open to discussing the practice and impact of RWE on regulatory review in Japan, Ohsawa explained, and recognizes that continuous and collaborative discussion by multifunctional stakeholders is necessary for its full utilization.