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Serving the best overall interests of the patient: All-inclusive approach to medicine based on the most advanced science and technology

Introduction

Throughout my clinical practice experience, I have always believed that medical care must be administered on the basis of the most rational judgments possible.

“Rational Medicine” is the idea behind creating a patient-centric system — a system which provides optimal medical care, based on the latest scientific knowledge, from the patient’s point of view — from the perinatal to the final stages of life. I strongly feel that this idea should always be the first consideration of health care professionals, companies, government authorities, and all other concerned parties.

In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) is proud to be a key player among these parties. As described in the Mission Statement I made public upon assuming the post of Chief Executive, PMDA strives to conduct its review, safety and relief service operations based on its mission “to protect public health and the lives of our citizens,” to “develop its human resources so that they possess the latest expertise and wisdom in their areas of expertise,” and to combine their strengths so as to “make thoroughly appropriate, science-based judgments on the efficacy and safety of medical products.”

In seeking to make this holistic approach to medicine — an approach which considers the whole spectrum of considerations, not just the specialist’s view from a defined area of expertise, in order to serve the best overall interests of the patient — the norm, PMDA is pursuing two more specific aims. The first is to provide better insight into the benefit-risk balance of drugs, medical devices and regenerative medical products by furthering regulatory science. The second is to create a medical environment in which the care provided is strictly evidence-based. Under this approach, patients will receive optimal medical treatment, including treatment based on innovative new technologies which have just become available. To these ends, PMDA will continue initiatives in the following four areas throughout 2017. As a result, I hope to accelerate the date when the public can begin to enjoy the benefits of this “Rational Medicine” approach.

1. Innovation through product approval reviews characterized by enhanced rigor and rationality
2. Further promotion of regulatory science
3. Increased sophistication of safety measures through the use of real-world data
4. Enhanced international partnerships.

This article will primarily focus on (1) and (2).

Innovation through Product Approval Reviews Characterized by Enhanced Rigor & Rationality

In 2014, PMDA recorded the world’s shortest median review time with regard to new drug product applications, even shorter than the European and US regulatory authorities. This level was reduced even further the following year; in addition, the “device lag” affecting the availability of “brand-new” medical device products has been virtually eliminated.

Looking to the future, it is crucial to enhance the rigor and rationality, in addition to the emphasis on speed, with which reviews are conducted. In October 2016, PMDA began to accept clinical data supporting new drug applications in electronic form, and to utilize these data not only for these individual product reviews but in anticipation of future formulation of disease-specific guidelines and other purposes. PMDA aims to further enhance the speed, rigor, and rationality of product reviews in accordance with the 2014 “Cooperation Plan to Accelerate Reviews of Medical Devices” and to advance discussions with the Ministry of Health, Labour, and Welfare (MHLW) concerning early approval modalities.

Consultations between industry and regulatory authority prior to product review application are important for enhancing the rigor and pace of innovative product reviews, particularly at the early development stages. PMDA plans to further enhance its Pharmaceutical Affairs Consultations on R&D Strategy and other consultation services and will strive to further shorten review times in 2017 through the SAKIGAKE (Global Front Runner) Designation System.

Furthermore, in October 2016 PMDA set up a Preparatory Support Office for the Practical Application of Innovation Gains (Inobeishon Jitsuyouka Shien Junbishitsu), which will begin work in earnest in April 2017, in response to the proposal to “establish an ‘MHLW-wide’ venture firm support structure” contained in the July 2016 report from the Advisory Panel on Venture Companies Supporting Innovation in Medicine (Iryou no Inobeishon wo Ninau Benchaa Kigyou no Shinkou ni kansuru Kondankai), convened by the MHLW Minister.

Further Promotion of Regulatory Science

PMDA has advanced a variety of innovative regulatory science policies, such as the Pharmaceutical Affairs Consultations on R&D Strategy, the formation of a Science Board, implementing the SAKIGAKE Designation System, Comprehensive Collaboration Agreements (with overseas counterpart agencies), a collaboration agreement with the Japan Agency for Medical Research and Development (AMED), and cross-sectional standards development. It will continue in this vein inter alia by establishing a Regulatory Science Center in 2018. This Center will actively promote “Rational Medicine” in regulatory science via collaboration with medical practitioners and academia; its goals will include formulating guidelines which encourage optimal use of novel medical products with innovative mechanisms of action.

PMDA’s Science Board, which entered its third term of activity in 2016, began discussing the following three areas to reinforce the foundations of regulatory science and will deepen deliberations on these topics in 2017 to contribute to the introduction of innovative medical technologies:

Suitable methodologies for clinical assessment of rare diseases

Rare cancers are an important example of diseases with particularly small patient populations, which severely limits the possibility to evaluate the efficacy of drugs through comparative studies. To support future clinical development activities in these areas, the Board will review the current status and clarify possible methods of clinical assessment.

Issues in new drug development (by academia in particular)

The Board will review current bottlenecks in drug development and suggest corrective action to benefit future product reviews, including the application of new nonclinical methodologies pertaining to efficacy and safety assessments that use disease model cells (e.g., iPS cells).

Medical applications of artificial intelligence

Expectations have risen in recent years on the practical use of medical devices and related software which function with artificial intelligence (AI). As the application of AI-related technologies to medicine could take various forms, the Science Board will: (a) review and analyze the current status and limitations of R&D using such technologies; and (b) discuss from a scientific perspective the challenges in promoting the practical application of these technologies to medicine.

Increased Sophistication of Safety Measures through use of Real-World Data

PMDA continues to advance its MIHARI (Vigilance) Project, quantitative assessment of adverse event risk through pharmacoepidemiological methods utilizing data electronically generated and stored by medical institutions.

PMDA has been developing its Medical Information Database Network (MID-NET), 23 hospitals in ten sentinel sites throughout Japan, as one of the databases to be used in this project since 2011. Each sentinel site will establish a database of ordering data, laboratory data, claims data, diagnosis procedure combination (DPC) system and other data types, which PMDA will integrate into an analytical system that can extract and parse data in a tailored manner to meet specific purposes and then compile and analyze the results. Data analysis testing has begun in preparation for full-scale operation beginning in 2018.

Enhanced International Partnerships

Based on the “PMDA International Strategic Plan 2015,” PMDA continues to promote information sharing/public communication and international cooperation while sustaining its contributions to regulatory harmonization activities between different nations and regions. In this context, PMDA opened an Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (PMDA-ATC) in April 2016. The PMDA-ATC has offered seven training programs to date, including a GMP seminar and seminars in Thailand and Taiwan on drug product review and other topics.

PMDA is actively engaged with international regulatory coordination activities at the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the International Medical Device Regulators Forum (IMDRF), and other fora. PMDA Japan will host the 12th Summit of Heads of Medicines Regulatory Agencies in Autumn 2017.

Approving new drug and medical device products in the world’s shortest review times and making them accessible to doctors and to patients is a crucial aspect of providing patients with cutting-edge, innovative medical care. I am deeply proud of PMDA’s contribution to this effort.

Parallel to swift approvals of these products, ensuring that they are optimally used from the patient’s point of view from the day they become available is of the essence to make “Rational Medicine” the prevalent norm. Cutting-edge, innovative medical care by definition lacks a record of real-world administration. We must work harder than ever to pool our collective wisdom regarding these new technologies to identify the most rational methods of product evaluation, and then promote the most rational use of these technologies (in terms of designated indications, regimen, and method of use) so they deliver optimal treatment benefits.

I am confident that Japan’s efforts to promote “Rational Medicine” through PMDA’s International Strategic Plan will transcend borders and benefit patients around the world. PMDA will deliver its utmost efforts so that “Rational Medicine” based on the rigorous application of regulatory science becomes the prevalent norm.

This article originally appeared in the April 2017 Global Forum.