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Establishing Safe and Expedient Clinical Application of New Highly-advanced Medical Technologies for Patients’ Peace of Mind

Institute for Medical Regulatory Science, Organization for University Research Initiatives

Professor Mitsuo Umezu of the Faculty of Science and Engineering, serving as the Director of the Institute for Medical Regulatory Science

Medical care is making rapid progress in the wake of recent breakthroughs in science and technology. However, translation of these breakthroughs into the latest medical treatments in an expedient manner while promising patient safety and reassurance is extremely difficult. While patients may benefit from a new medical technology, it is ethically unfeasible to apply any new technology in the clinic before ensuring its safety and efficacy. To date, the development process has been mandated by scrupulous preclinical and clinical trial and study protocols where the product is tested on animals as well as human volunteers. Although exceptional provisions exist for pharmaceutical products or medical devices in cases of societal emergencies, in general sufficient data needs to be collected and verified in accordance with stringently defined testing procedures. This process can take up to 20 years from development through manufacturing and acquisition of marketing approval. How can this process be streamlined?

In contrast to scientific technological advancements, establishing and training experts in the practical application of new medical technologies lags surprisingly far behind. A unique and major challenge to this field is adjusting the criteria for determining value among diverse interested parties that may include scientists, medical practitioners, industrialists, governments, lawyers, ethicists as well as patients. Hence, the pressure to harmonize scientific and ethical standards to allow the proper judgements to be made in different circumstances co-exists with the need to establish and develop reliable evaluation techniques.

Founded in October 2013, The Institute for Medical Regulatory Science approaches these issues from a comprehensive perspective by performing tasks that range from formulating guidelines for advanced medical treatment—based on the foundations of life and medical sciences or medical engineering—to developing professional human resources. In October 2015, this organization adopted the strategic research initiative: “Realizing a safe 21st century society with peace of mind and improved quality of life”, and started full-scale organizational development as a basis for the Organization for University Research Initiatives. We interviewed Professor Mitsuo Umezu of the Faculty of Science and Engineering, who serves as director.

Establishing a State-of-the-Art Professional Graduate School

Photo: Lecture at the Cooperative Major in Advanced Biomedical Sciences in the Graduate School

“During my long-term engagement in the field of medical engineering and artificial organs, on two occasions I witnessed the application of ventricular assist devices in humans, technically known as First in Human (FIH). The first time was in 1982 when I was a researcher at the National Cardiovascular Center that had just been established. The second time was in 2005, in a clinical application procedure in collaboration with Tokyo Women’s Medical University. Despite adequate simulations in a mechanical model of the cardiovascular system as well as animal experiments, I was still concerned if it would function effectively in a human body. This concern, which caused me lack sleep and nightmares, made me think we must strive to eliminate such anxiety for the next generation of researchers. Unless we ease the regulations and work environment conditions, I fear that the number of researchers willing to engage in the practical application of promising technologies will not increase.” (Professor Umezu)

The number of papers accepted by the top journals in the field of clinical medicine, such as New England Journals and Lancet, ranks around 20th in the world, falling far below the number of papers accepted by prestigious scientific magazines, such as Nature or Science, in the research of basic medicine in Japan. This indicates that the connection between basic research and clinical medicine is overwhelmingly weak. Similarly, in terms of the practical application of medical equipment, Japan leads the world in mensuration and diagnostic equipment but lags behind when it comes to equipment used for medical treatment.

“Although I had been bothered by these facts for quite a while, Professor Hiroshi Kasanuki (former Director of the Heart Institute of Japan, Tokyo Women's Medical College) and Professor Yasuo Ikeda (former Dean of Keio University, School of Medicine) introduced me to the field of regulatory science. It was then that I thought this is exactly where we should focus. Hence, in 2010 we jointly established the Cooperative Major in Advanced Biomedical Sciences (Doctoral Program) specializing in medical regulatory science between Waseda University and Tokyo Women's Medical University. Much to my surprise, many professionals with experience in related fields subsequently entered the program one after another. Governmental administrative officers, surgeons, core members of global corporations and startup companies, and even faculty members of medical colleges enrolled in this program. while those who are eligible to join academic staffs came to this new Graduate School to study. In the four years since its establishment, as many as 30 people have obtained doctorate degrees. Incredibly, some students have come all the way from Kyushu and even from Silicon Valley to attend lectures on Saturdays each week. This has made me realize the extent to which this field of instruction had been eagerly awaited.” (Professor Umezu)

Establishing “Non-Clinical” Evaluation Methods

Figure 1: In the government’s Project for Promoting Innovative Pharmaceutical Drugs/Medical Devices/Regenerative Medicine for Practical Application (2012–2016), the Center for Advanced Biomedical Sciences, to which the Institute for Medical Regulatory Science belongs, was adopted as one of the bases along with the national universities that were former imperial universities and national hospitals (source: Ministry of Health, Labor and Welfare material).

Dr. Mitsuru Uchiyama has worked at the National Institutes of Health Sciences (NIHS), and is known to be the first in the world to have proposed the concept of regulatory science, in 1987. He defined regulatory science as: “the science of regulating scientific and technological developments to be in their most desirable forms that truly benefit humans and society.” About a quarter-century later, in August 2011, as part of the fourth Science and Technology Basic Plan of Japan, adopted at a cabinet meeting after the Great East Japan Earthquake, a system of reform for promoting life enhancement was listed as one of the pillars to prepare for the hyper-gerontological society to come. Furthermore, improving and strengthening regulatory science in the areas of pharmaceuticals and medical devices were precisely set out as government policy. In accordance with the Plan, the initiative to establish the joint graduate program was implemented in a timely manner.

Following inauguration of the Graduate School, a research institute was also organized. Currently, there are 17 internal researchers and 20 adjunct researchers affiliated with the institute, divided among five teams in specialized areas: 1) benefit/risk assessment after a medical device is approved; 2) benefit/risk assessment in FIH applications of medical devices; 3) benefit/risk assessment as a post-sales safety measure for medical devices; 4) cost-benefit assessment and medical technology evaluation of medical devices; and 5) venture capital theory development for medical devices.

The institute also participates in national projects promoting practical applications of medical devices, and plays an important role in developing practical application guidelines in the fields of medical devices and regenerative medicine (Figures 1 & 2). The Institute has earned the deep trust of the Ministry of Health, Labor and Welfare as well as policy-making bodies of the government such as the Pharmaceuticals and Medical Devices Agency (PMDA).

Figure 2: Concept of medical regulatory science as an evaluation science.

“The keyword is ‘non-clinical.’ We seek to establish regulatory science as an academic discipline by establishing non-clinical methods, namely, evaluation methods that replace or supplement experiments on human subjects.” (Professor Umezu)

Figure 3: The optimal stenting method for a stent graft (a new type of artificial blood vessel in which a stent—a spring-like metal device—is attached to an artificial blood vessel)

Powerful tools for achieving a non-clinical approach include engineered devices such as blood circulation simulators, which Professor Umezu and his fellow researchers have been working on for a long time. These methods feature advanced medical engineering. For instance, blood is a living matter whose fluid dynamic properties is constantly changing—sometimes becoming thin, sometimes thick. A simple hydrodynamic model cannot simulate the characteristics of blood, and developing a mechanical model of the circulation system would be insufficient. It is necessary to repeat trial and error, such as actually having animal blood flow-pressure relation under several diseased condition, to test blood flow in the circulatory system.
We have also established an accelerated durability test method for stenting, which is an innovative intra-vessel treatment that expands and retains blood vessels through the insertion of devices made of metal or other materials. Durability data has been obtained from a testing period much shorter than the time required for the actual procedure (Figure 3). Professor Umezu calls such methods ‘engineering-based medicine’.

The greatest strength separating regulatory science from other disciplines is that it not only involves abstract concepts, but also practical guidelines that stipulate the types of evaluations and experiments or methods to be implemented. The history of collaborative research in medical engineering at Waseda University has also been a history of pursuing medical regulatory science. Future developments at the Institute for Medical Regulatory Science, in which all of its accumulated knowledge will be utilized, is much anticipated.

Related links

Institute for Medical Regulatory Science, Waseda University
Center for Advanced Biomedical Sciences, Waseda University
Tokyo Women’s Medical University/Waseda University Cooperative Major in Advanced Biomedical Sciences (Japanese text only)
Organization for University Research Initiatives, Waseda University
Faculty of Science and Engineering, Waseda University