Evolving Acceptance and Use of RWE for Regulatory Decision Making on the Benefit/Risk Assessment of a Drug in Japan

Abstract

There is growing interest in the utilization of real‐world data (RWD) and real‐world evidence (RWE) for regulatory purposes. However, there are challenges in the practical utilization of RWD to provide RWE as a basis for regulatory decision making. This article presents the regulatory initiatives in Japan and efforts taken to promote the utilization of RWD/RWE for regulatory decision making at the pre‐ and postapproval stages of a drug. There has been a rapid increase in the number of RWD cases evaluated for drug safety assessment in Japan. Nevertheless, more regulatory experiences and considerations are necessary for the utilization of RWD in the efficacy evaluation of a drug. Based on past experiences, data reliability and appropriateness of the methodology for analysis are the major discussion points in utilizing RWD and RWE for regulatory decision making. International harmonization of regulatory requirements is another important area in utilizing RWD and sharing the RWE globally. We describe our perspective on providing RWE, which is useful for regulatory decision making throughout a drug’s life cycle.

Real world data and data science in medical research: present and future

“…In drug development, pharmaceutical companies and regulatory authorities consider utilizing an external control arm for a non-randomized clinical trial of a single arm when randomization may not be feasible or ethical (Nishioka et al, 2021 ; US Food & Drug Administration, 2018 ) Bias is greater problematic in comparison between treatment arms from clinical trial and the RWD, than the comparison between treatment arms within a database of the RWD. However, there is a strong need of the external control arm in rare disease area, and regulatory guidance has been issued in several countries.…”

“…In Japan, the Ministry of Health, Labour, and Welfare (MHLW) and the Pharmaceuticals and Medical Devices Agency (PMDA) have been working to promote the RWD use for regulatory decision making. They have issued several guidelines, including the RWD use for post-marketing surveillance and registry data use for drug applications (Nishioka et al, 2021 ; Ishii et al, 2021 ).…”

Multi-Criteria Decision Analysis for Benefit-Risk Analysis by National Regulatory Authorities

“…The use of structured benefit-risk evaluations by NRAs has increased in line with the maturing of the benefit-risk science ( 7 – 9 ). In 2012, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human use (ICH) updated the Periodic Safety Update Report (PSUR) to the Periodic Benefit-Risk Evaluation Report (PBRER), which placed greater emphasis on the determination of the benefit-risk assessment for medicines, rather than just acting as a safety update report ( 10 ).…”

Real-world data: general regulatory approaches in the EU and Japan

“…Более того, обновлённая Стратегия возрождения Японии, принятая в 2015 году, стала стимулом для внедрения новых методов исследований, в частности, путём создания специализированной инфраструктуры на основе информации, содержащейся в реестрах заболеваний [13]. Ссылаясь на необходимость использования реестров, включая реестры заболеваний и реестры продуктов, при разработке лекарственных препаратов в случаях, когда традиционные рандомизированные клинические исследования невозможны (например, для орфанных препаратов), Управление лекарственных средств и медицинских изделий Японии в марте 2021 года разработало: «Основные принципы использования реестров для подачи заявлений» и «Вопросы, которые следует учитывать для обеспечения надежности при использовании данных реестров при подаче заявлений» [14].…”

“…Использование данных реальной клинической практики в целях оценки безопасности или эффективности препарата со стороны уполномоченного органа также допускается в рамках процедуры условной регистрации препарата, введённой в 2017 году, что получило официальное закрепление в Законе об обеспечении качества, эффективности и безопасности продукции, включая лекарственные препараты и медицинские изделия, в 2020 году [15].…”