In the present study, we investigated the characteristics of old drugs which have been and are still used widely in clinical practice in Japan, from the aspect of clinical usefulness and convenience. We defined drugs which obtained Japanese marketing authorization in or before 1999 and had sales over 10 billion Japanese Yen in 2013 as “long-selling drugs”. Competing products of each long-selling drugs were also picked out. Of the 154 drugs which had sales over 10 billion Japanese Yen in 2013, 58 drugs (38%) were long-selling drugs. For long-selling drugs, proportion of drugs with a mechanism of action which was recommended as a first-line therapy in the treatment guidelines was larger than for competing drugs. When we compared the characteristics among drugs with same mechanism of action, long-selling drugs had abundant clinical study results in their package inserts compared with competing drugs. Additionally, proportion of drugs with post-marketing clinical study results cited in the treatment guidelines was larger for long-selling drugs compared with competing drugs. Long-selling drugs had smaller number of doses per day than competing drugs. It is important to utilize long-selling drugs, which have abundant clinical evidence and are also inexpensive relative to newly marketed drugs, from the viewpoint of controlling medical expenditure as well as providing healthcare with quality and efficiency.

In the present study, we investigated differences in the proportion of geriatric patients between in clinical practice and in clinical trials. We also investigated information about drug treatment in elderly patients which were provided in package inserts to consider better drug development strategy and provision of information for geriatric patients. Diseases commonly found in the elderly were selected based on the Japanese guideline for medical treatment and its safety in the elderly 2015, and all the new drugs (new active substances and drugs with new indications) approved between April 2010 and March 2016 in Japan with the indication for the selected diseases were picked out. For each of these drugs, number of total subjects and geriatric subjects which were enrolled in clinical trials were collected based on disclosed documents. We also investigated age distribution of patients of the selected diseases in clinical practice based on a public report of patient survey 2014. Proportion of geriatric patients in clinical trials was smaller than that in clinical practices. Furthermore, degree of the gap was small in patients aged between 65 and 74, and it was large in the elderly aged 75 or over. Almost all the information about drug treatments in geriatric patients provided in package inserts was for calling caution with stereotypical comments in accordance with the notification from Ministry of Health, Labour and Welfare. There were few drugs of which measures for safety concerns were provided in its package insert. It is important to collect and evaluate clinical efficacy and safety of new drugs in geriatric patients during the development phase, and at the same time, to appropriately and continuously provide the latest information to medical personnel through monitoring their use in geriatric patients in clinical practice and providing knowledge that there is little difference in medication between elderly and non-elderly patients.

The price of antibody agents for cancer treatment in Japan has increased significantly in the past few years. This has had a severely negative impact on National Medical Care Expenditure (NMCE), necessitating that drug prices be revised outside the standard schedule. In Japan, new drug prices are calculated based on the cost accounting method if there are no drugs with similar indications and modes of action, and after that the calculated price are reviewed and approved by the Central Social Insurance Medical Council (Chuikyo). We surveyed the Chuikyo reports and the Pharmaceuticals and Medical Devices Agency (PMDA) review reports from Oct 2004 to Aug 2016, and extracted 30 antibody cancer drugs to investigate the factors contributing to the drug price or the total product cost, which makes up a large part of the drug price. We found that a lower peak sales forecast upon submission of an application for antibody drug price by a sponsor was significantly associated with a higher cost for 1-month treatment, while a lower research expense for antibody drug development also showed a significant tendency to increase the cost of 1-month treatment. The former finding regarding the effect of a lower peak sales forecast could be inferred by the cost accounting method, but the latter result regarding the effect of lower research expense could not be fully explained due to the undisclosed breakdown of total product cost. Our results indicated that this missing information would be critical for appropriate drug pricing. To establish fair and clear drug pricing, including that by revised timing, the total product cost (especially the amortized plan of research expense) must be disclosed, and upon each application to add an indication for a particular drug, an amortized plan for each and/or all indications should also be developed and reviewed to determine an appropriate drug price after the additional approval.

After discussion at the International Meeting of World Pharmacopoeias from 2012, in May 2016, the WHO announced and published the Good Pharmacopoeial Practices (GPhP) guideline which is briefly describing the role and significance of existence of pharmacopoeia, basic philosophy of creating pharmacopoeia’s monographs for API, excipients and final drug products, notes, contents of composition, procedures of preparation etc. at a high level. In order to promote dissemination to the stakeholders of the Japanese Pharmacopoeia and to make use of it, we will report on the background of its preparation of this guideline, contents of description, points to be noted and future issues.

In general, randomized controlled trials (RCTs) provide us the best evidence of a treatment. However, it is almost impossible to conduct an RCT in areas such as rare diseases, intractable diseases and medical devices. Moreover, in some post-marketing circumstances, evidence from RCTs is not well generalizable to other patient populations. Therefore, the real-world evidence of the treatment in broad patient groups is required to support decision-making in clinical practice and public health policy. There are several ways to utilize real-world data; data sources for a prevalence/marketing survey, a feasibility survey of a clinical trial, a survey of possible patients to be enrolled in the clinical trial, a survey for designing the study protocol, a post-marketing surveillance study, and an external control group. There were some examples of demonstrating evidence of efficacy of an intervention by combining clinical trial and patient registry data. This paper explores tips for effectively utilizing real-world data, e. g. use not a historical control but concurrent control, adjust for confounding by indication, and identify the real-world data sources when developing a trial protocol. The new rigorous study designs utilizing real-world data will be enhanced. In the current situation, patient cohort-based trials may provide best evidence as the synthesis of a thesis (RCT evidence) and its antithesis (real-world evidence).

SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting lung/gastrointestinal cancer patients to 40 sponsor-/investigator-initiated registration trials in collaboration with 15 pharmaceutical companies and 245 hospitals. During the first period between February 2015 and March 2017, a total of 4,800 patients have been enrolled. Genomic profiling of each cancer were analyzed and new drug applications for label expansion are in preparation based on the results of several registration studies. In addition, on-time clinical-genome data sharing with industries and academic institutions and registry study for new drug evaluation as a historical control data have already initiated, which will facilitate new agent development in Japan. In the registry study, three approaches are indicated for the purpose of historical control data at a new agent evaluation in regulatory authorities: retrospective data of the patients enrolled for completed registration study, prospective registry data collection for orphan-fractionated population, and parallel data collection along with new investigator-initiated registration study. With the outcome data of both developmental studies and registry, establishment of precision medicine in Japan is anticipated.

MID-NET^® is the closed network system of Electronic Medical Records (EMRs) databases which consists of 10 medical institutions including 23 hospitals in Japan. The aim of the MID-NET^® is to promote effective safety measures for drugs through pharmacoepidemiological studies utilizing real world data. The MID-NET^® is a distributed database with the common data model which are placed in each hospital. In 2018, the database is expected to include approximately 4 million patients’ information, such as diagnosis, medical procedures, prescription drugs and laboratory test results since 2009. Every piece of information is mapped to common codes among all hospitals. The high data quality of MID-NET^® was confirmed by checking consistency between original data and MID-NET^® database. Users can access and analyze MID-NET^® databases through an on-site center. PMDA has conducted several pilot studies for benefit-risk assessments. We are on final stages for implementation in FY2018 and working on creating utilization rule and discussion of user fee with industries and academia.

Real World Data (RWD) is an essential tool for pharmaceutical industry not only for commercial/marketing purposes but for unmet needs seeking, clinical trial designing (e. g., endpoint validation, patient segmentation) efficient country/site allocation and patient enrollment for clinical trials, patient safety surveillance, health-technology assessment and outcomes researches. Administrative datasets (e. g., claims) are primarily used because of their accessibility and size but EMR and patient registries can also be useful. In this summary article, current activities on RWD and perspective from the industry are illustrated. A questionnaire survey in 2015 suggested that around half of the companies already had an access to Japanese datasets. Indeed, many studies using Japanese datasets have already been published by industry researchers with and without collaboration with academic parties. Data Scientists in industry, regulatory authorities and academia shared their insights on clinical trial design using RWD at Data Science Round Table, especially on business cases for internal decision making. These examples are particularly valuable since they are not always published. RWD for safety studies are one of the hot topics since database studies will be an option of Post-Marketing Surveillance from FY2018. Nonetheless, it is still critical to note that any studies should be designed for purpose and one size does not fit all. National Database (NDB) covers almost entire population and can be a useful tool for epidemiology researches. Although industry does not have a direct access to NDB, several monthly summary tables are created on our request and will be published. The results will also be useful as a reference for external validation of commercially available datasets.