Proceedings: DIA 2018 Global Annual Meeting

Utilizing Real World Data: A PMDA Perspective

Yoshiaki Uyama
Director, Office of Medical
Informatics and Epidemiology,
Pharmaceuticals and Medical
Devices Agency


or some time, regulatory agencies have explored safety surveillance methods using real world data (RWD) and conducted real world studies of post-marketing safety concerns to inform regulatory decisions. The session “Regulators’ Utilization of Real World Data in Pharmacovigilance Activities” focused on the approach of the US Food and Drug Administration (FDA), European Medicines Agency (EMA), Health Canada, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) as well as the challenges faced in exploring new methods and in designing and conducting these studies. The panelists also discussed future areas of research, including opportunities for international collaborative research. This article summarizes the key takeaways from the perspective of PMDA.

Key Takeaways

  • PMDA has utilized RWD for drug safety assessment since 2009.
  • Recently, Japanese regulations were updated, including a publication of guidelines, for promoting RWD utilization by pharmaceutical industries in pharmacovigilance. (Available here in Japanese only.)
  • Several challenges have been identified in utilizing RWD for regulatory purposes, including data quality, data coding, deep understanding about databases, validation of clinical outcomes and system infrastructure, timely and continuous communication with marketing authorization holders (MAH), and active collaborations among all stakeholders.
  • Continuous sharing regarding experiences and knowledge among regulatory agencies and other stakeholders will be necessary to recognize common challenges toward international harmonization in utilizing RWD in the regulatory process.

Regulatory Update for Promoting RWD Utilization

PMDA has worked to promote utilization of RWD such as electronic medical records (EMRs) and data of patient registries for drug safety assessment. In order to promote RWD utilization by pharmaceutical companies, the ministerial ordinance (Good Post-Marketing Study Practice, or GPSP) was amended in October 2017 and implemented on April 1, 2018. The related guidelines were also published recently, such as Basic Principles on the Utilization of Health Information Databases for Post-Marketing Surveillance of Medical Products (June 2017), General Steps for Considering a Plan of Post-Market Studies of a Drug (January 2018) and Points to Consider for Ensuring Data Reliability on Post-Marketing Database Study for Drugs (February 2018). MID-NETⓇ (Medical Information Database Network) was also formally launched on April 1, 2018, meaning that pharmaceutical industries and academia, in addition to PMDA and cooperative hospitals, can now utilize this database.

Challenges in Utilizing Real World Data for Drug Safety Assessment

Based on our experiences utilizing RWD, several challenges have been identified:

  1. Assuring data quality in a database. High data quality is a prerequisite for utilizing RWD. Thus, consistency between the data stored in the database and the original data (i.e., EMRs) should be checked and confirmed before utilization. The data coding process should also be standardized across all sites contributing to a database.
  2. A deep understanding of data characteristics and real situations of medical care in clinical practice. This deep understanding is very important for planning and designing a study that utilizes databases. It will help select the most appropriate database, design the study, and identify appropriate factors for controlling confounding variables for achieving a study objective.
  3. Validation of clinical outcome and system infrastructure. Clinical outcomes should be properly validated in order to identify a clinically meaningful event in a database.
  4. Timely and continuous communication with marketing authorization holders. Effective communication with these stakeholders is crucial to discuss the strategic use of RWD in pharmacovigilance, including database selection, design, analysis plan, timing and expected safety measures.
  5. Active collaborations among all stakeholders. RWD utilization is still at the learning stage, and extensive collaboration will be a key success factor. There are a lot of matters which need to be further discussed and considered. Examples are PMDA-academic collaborations with clinical outcome validation studies to establish a reliable outcome definition more efficiently. PMDA has also shared experiences with other regulatory agencies under the ICMRA (International Coalition of Medicines Regulatory Authorities) framework and via bilateral communications.

Session Panelists
Michael Blum (Moderator), Deputy Director, Office of Pharmacovigilance and Epidemiology, CDER, FDA
Rhonda Kropp, Director General, Marketed Health Products Division, Health Canada
Michael D. Nguyen, FDA Sentinel Program Lead, FDA
Agnès Saint-Raymond, Head of International Affairs, Head of Portfolio Board, European Medicines Agency (EMA)
Yoshiaki Uyama, Director, Office of Medical Informatics and Epidemiology, Pharmaceuticals and Medical Devices Agency (PMDA)

The Next Step

To promote the use of RWD for regulatory purposes, we need to continue sharing experiences and knowledge among regulatory agencies and other stakeholders. Such efforts may facilitate the recognition of common challenges that should be considered at a global level. For example, with an internationally standardized or compatible common data model, results could be shared beyond databases. International harmonization efforts will also drive the use of RWD. International guidelines focusing on some specific areas, such as strategic considerations of RWD utilization in drug development, data reliability, coding standards, analytical approaches, or format of protocol/report for regulatory submission, could be discussed in the near future.

The next five years will be an important period for considering the use of RWD to support regulatory processes. More active discussions in this area are expected, and PMDA looks forward to further international collaborations in utilizing RWD for better regulation of drug life cycles.