A retrospective study to review the listed new drugs that obtained premiums under the drug price calculation was conducted and the factors which affect the assessment for premiums and upward adjustment were investigated. Four hundred and sixty four drugs were listed in the NHI price list from October 2004 to December 2014. The NHI drug price was calculated by the similar efficacy comparison method for 285 drugs (61.4%), while 135 drugs (29.1%) were calculated by the cost accounting method. Of the 285 drugs assessed by the similar efficacy comparison method, 89 (31.2%) received premiums for usefulness. Of the 135 drugs priced by the cost accounting method, the operating profit percentage of 33 drugs (24.4%) was adjusted upward. The drugs with a new mechanism of action had more chance to get premiums for usefulness than the other drugs (p<0.0001). Furthermore, the drugs with clinical trial results which demonstrated its superiority to an active control drug had more chance to get premiums for usefulness than those which showed non-inferiority to an active control drug (p=0.0013) and those which demonstrated superiority to a placebo control (p=0.0046). Similarly, compared with the drugs for which only single-armed clinical trial (s) was conducted, the drugs for which a clinical trial with an active control was conducted were likely to be adjusted the operating profit percentage upward (p=0.0021). The range of premium rates varied widely.

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New drug development has become globalized and the number of multi-regional clinical trials (MRCT) including Japan has increased year after year. It is well known that some ethnic factors may influence the efficacy and/or safety of drugs, and in the guideline “Basic principle on global clinical trials” the Ministry of Health, Labour and Welfare of Japan requests sponsors to evaluate effects of ethnic factors specific to individual regions on efficacy and safety of investigational drugs when conducting an MRCT. However, it may often be hard to identify what ethnic factors influence efficacy and/or safety of investigational drugs because it depends on the type of drug, the target disease, the trial design, the regions where the trial is conducted and various other factors. In our research about ethnic factors for several diseases based on the review reports published by the Pharmaceuticals and Medical Devices Agency, we found that inconsistencies in results of MRCT between regions were caused by imbalance of some ethnic factors considered to be covariates or risk factors between the regions. No ethnic factor which influenced only a specific region was found. This means that the 3-layer approach proposed by Komiyama et al is reasonable to evaluate data from an MRCT, and in addition to subgroup analyses we should use a statistical model that includes appropriate ethnic factors to estimate the efficacy and safety of investigational drugs in a specific region. We also emphasized that information about ethnic factors from MRCTs be continuously accumulated to identify what ethnic factors influence the efficacy and/or safety of drugs.

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Currently the medication history management and guidance fee under the medical insurance system has been charged based on a paper-form medicine notebook. We conducted a questionnaire survey on pharmacies to reveal a variety of data contained in both of a paper-form medicine notebook and an electric-form one. Also we conducted another survey to explore patients attitudes toward a medicine notebook. Of 1,000 pharmacies, 547 pharmacies returned their responses. Though all of the responded pharmacies utilized a paper-form medicine notebook, only 15.9% of them utilized a electric-form medicine notebook with a paper-form one. Of 307 patients, 227 patients returned their responses. Only 0.5% of them utilized a electric-form medicine notebook. A variety of data really utilized in an electronic-form medicine notebook were less than that in a paper-form one. 20.9% of the responded patients answered that they wrote in a medicine notebook by themselves, about their blood pressure, a change of their health conditions, etc. Though almost half of them would like to show their own medicine notebook to any health professionals, the other half of them would like to show a medicine notebook only to the health professionals they would like to show. Therefore, in order to introduce an electronic medicine-notebook in the current medical insurance system, it is necessary for an electronic-form medicine notebook to restrict medical professionals reading of a medicine notebook depending on a patient’s decision, to cover the same variety of data covered in a paper-form one, etc.

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To develop a residency curriculum dedicated to training qualified pharmacists to coordinate and cooperate with other healthcare professionals in team-care settings, we compared curricula of the long-standing postgraduate year-2 residency program (oncology) of the American Society of Health-System Pharmacists (ASHP) with the Japanese residency program for pharmacists specializing in oncology of the National Cancer Center Hospital (NCCH) of Japan. We thereby identified challenges of the residency program for the training of specialist pharmacists, and focused on areas deemed necessary to foster qualified pharmacists to contribute to the team care. The results of the comparison showed that there were no substantive differences in the outcomes and goals of the curricula between Japan and the United States (US). The US curriculum, however, followed a much more consistent policy, and placed a greater emphasis on fostering the ability to optimize individual patient’s pharmacotherapy by making full use of “clinical reasoning”. We also conducted a questionnaire survey of NCCH residents and preceptors to identify specific areas for improvement in the curriculum. The results of the survey revealed the necessity of training with an emphasis on cultivating drug information collection/processing skills to enhance research abilities, particularly among the less-experienced residents in tackling clinical research, and standardizing residents’ and preceptors’ views on outcomes and goals. The challenges learned and the improvement plans generated from this study may have a wide applicability to other institutions or specialty areas in the context of developing specialist pharmacists.

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Regulatory science plays an important role to implement scientific approach for evaluating the benefit and the risk of medical products. That approach is important to obtain consensus from various stakeholders even at any steps of developmental, approval, or marketing step. Comprehensive study fields, ranging from basic to social science, must be dealt with, and rapid technological progress needs to be kept up with. Hence, it is strongly demanded to advance regulatory science through research and to cultivate human resources through education. In this article, we report up-to-date status of the research and education in EU and US regarding regulatory science. In US, the most noticeable change was the expansion of the Center of Excellence in Regulatory Science and Innovation (CERSI) to the west coast in 2014. This expansion is made because many venture companies of biotechnology and of information and communication technology are located there. This represents that Food and Drug Administration (FDA) is aware that those companies are next key players in the medical fields. In EU, European Medicines Agency (EMA), acts differently from FDA ; i. e. financial support is strictly excluded, although EMA does participate in collaborative research activities. Instead, EMA puts the strong emphasis on the educational training to equalize the regulatory levels among EU countries in terms of the quality, safety, and efficacy of medical products. It was uniqueness that appeared from our inquiry about how the two biggest regulatory bodies in the world promoted research and education of regulatory science. It is our expectation to learn from their examples so that we also pursue unique, but globally compatible, Japanese-way of promoting regulatory science.

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In Japan, the drug price calculation criteria is applied to determine the price of drugs based on the National Health Insurance (NHI) Drug Price List (NHI Price List) proposed by the Central Social Insurance Medical Council (Chuikyo). NHI Price List affects the research and development strategy of a pharmaceutical company. We surveyed the Chuikyo-documents from October 27, 2006 to August 26, 2015. The number of approved new drugs was 792 and that of new compounds was 483. The number of new drugs whose prices were calculated based on “drugs of similar efficacy comparison-based price setting (Ⅰ),” “cost-based price setting,” and “drugs of similar efficacy comparison-based price setting (Ⅱ) ” was 473 (59.7%), 192 (24.2%), and 67 (8.5%), respectively. The number of new compounds belonging to therapeutic categories such as “other agents affecting metabolism,” “agents affecting central nervous system,” “antineoplastic agents,” and “cardiovascular agents” was 82 (17.0%), 57 (11.8%), 58 (12.0%), and 36 (7.5%), respectively. In the antineoplastic agent category, the prices of more than half the drugs were calculated based on “cost-based price setting.” The number of patients expected to take antineoplastic agents was low, whereas the expected drug price was high. In particular, very few patients were expected to take drugs marketed by a foreign pharmaceutical company whereas the expected drug price was high compared with that observed for drugs marketed by a domestic pharmaceutical company. These results provide a basis for the development and application of new drugs in Japan.

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AMED, established on April 1 2015, has been tackling to promote medical R&D and improve the environment for such R&D and implement subsidy activities based on “the Plan for Promotion of Medical R&D” for the purpose of integrated promotion of medical R&D from basic research to practical application, smooth application of outcomes, and improvement of the environment for medical R&D in a comprehensive and effective manner. AMED consolidates budgets for research expenses from three different Ministries, which enables to provide a one-stop service for research expenses. In other words, the unification of contact points and procedures for research expenses can be expected to reduce the administrative burden on institutions and researchers. AMED is also expected to carry out the following functions. 1) Implementation of R&D in healthcare area through AMED’s new program management system, 2) Improvement of the infrastructure for clinical researches, etc, 3) Support toward industrialization, 4) Promotion of global strategies. This article briefly summarizes the AMED’s activities so far, especially focused on the “Project for Japan Translational Research and Clinical Research and Trial Core Centers”, one of nine collaboration area projects, and new public private partnership activity, and also discusses the importance of “Regulatory Sciences of Medical Products” in order to achieve the AMED’s mission.

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Under considering pharmaceutical and medical device industries as a growth engine, the government of Japan has strengthened pharmaceutical and medical device research and development (R&D) with various measures including establishment of Japan Agency for Medical Research and Development (AMED) in April 2015. Also the government conquered ‘drug-lag’, redundancy of review term for new drug, and the fact contributes toward transparency and reliability of the R&D in Japan. Pharmaceutical manufacturers, thus, have changed their business behavior for concentration of their investment toward R&D, collaboration with academia, and globalization. These transformations give the government new opportunity for activating R&D. The past purpose of activation was mainly aiming for conquest of ‘drug-lag’, and the recent one is aiming for arousing innovation. The Sakigake review is one of the new approaches for breakthrough products. This article tries to introduce the scheme of Sakigake review and the background of R&D circumstance in Japan.

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Clinical Innovation Network (CIN) is a new collaboration scheme with National Medical Research Centers (NCs) and industries, which was proposed by Ministry of Health, Labor and Welfare in 2015. In CIN, each NC will make patient registries to search disease related information. Purpose of CIN is to facilitate clinical development in Japan by effective utilization of medical information from patient registries. Pharmaceutical companies will make a consortium with NC, and will be able to use the information from patient registries through the consortium activities. Pharmaceutical companies highly expect the CIN activity because patient registry will be useful for promoting the patient recruitment to clinical trials as well as for generating the reference data for clinical study protocols.

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The government of Japan made a nation-wide preparedness for innovative regenerative medicine, both research promotion and safety assurance. The regulatory guidelines for regenerative medicine have been reexamined and the revised Pharmaceutical Affairs Law (PAL), which was renamed as the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act), were implemented in Nov. 2014 in Japan. Based on these changes in the national framework for regenerative medicine in Japan, we would like to introduce the past, new and near-future approved regenerative medical products in this framework.

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Twelve years have already passed since the investigator-initiated clinical trials were introduced in Japan. From the fact that there are drugs and medical devices were approved based on the results of investigator-initiated clinical trials, it is considered that the results of introducing investigator-initiated clinical trials were steadily obtained. During this time, Good Clinical Practice (GCP) was amended to facilitate execution of the investigator-initiated clinical trials. As a result, surrounding environment such as supporting system and research funding was dramatically changed. In addition, experiences of investigators, Clinical Research Coordinators (CRCs) and clinical trial sites were accumulated greatly. The phase Ⅰ clinical trials for the seeds that Academia developed came to be conducted and it is considered that the investigator-initiated clinical trials are proceeding to a new stage. This review describes the progress and future topic of the investigator-initiated clinical trials.

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Twenty-five years have passed since the start of the International Council for Harmonisation (formerly the International Conference on Harmonisation ; ICH). The regulatory authorities and industries of Japan, the United States, and Europe worked together and published more than 80 ICH guidelines. Main deliverables are “Good Clinical Practice” (E6 guideline) and “Common Technical Document” (M4 guideline ; CTD) and they have contributed significantly to the drug development and new drug application procedure harmonisation. In such circumstances, global drug development and operation based on the paper, becomes large problem in cost, efficiency, and speed. Therefore, to convert clinical study related documents and regulatory documents from paper to electronic forms is one of the important ICH activities in recent years. Electronization in the procedure of life cycle of drug development (development to post-approval) has been discussed, change the document submission method to the authorities (gateway system) and electronic CTD (eCTD) transformed paper submission and review process. Also the electronic study data set for new drug applications (data from nonclinical and clinical studies), not only eCTD, can be submitted from industries, authority reviewers could analysis independently. Therefore, the drug evaluation having higher precision for the sake of patient became possible. As a result of the October 2015 ICH corporation, the scope of ICH activities became global (not only Japan, the United States, and Europe) ; post-marketing and generics are also included. It is expected that can be submitted as electronic documents to countries in the world, and to be able to contribute to the world’s patients. In order to put it into practice, we need to set detailed rules for handling of drug related information. ICH electronization activities will become more important to move it forward. Furthermore, the Japan Pharmaceutical Manufacturers Association (JPMA), as ICH founded organizations, will continue to incorporate the ICH guidelines into Japan ; spread them especially to the Asian region.

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