Acetaminophen is commonly used as the global standard of analgesics. For example, the WHO lists acetaminophen as an essential drug and various clinical guidelines in many countries include acetaminophen as a first-line drug for pain relief because of it's efficacy and safety profile. In particular, there is not significant risk of such as gastrointestinal disorders, renal dysfunctions, bleeding, or cardiovascular events, and it is considered to be a safer option than non-steroidal anti-inflammatory drugs(NSAIDs). In Japan, however, NSAIDs are widely used to treat pain while the use of acetaminophen for pain relief is quite limited. This difference could be attributed to the low approved dose of acetaminophen in Japan, which is less than half of that used elsewhere. This lower approved dose causes difficulty in obtaining analgesic effect with acetaminophen. In January 2011, however, the approved dose of acetaminophen in Japan was increased to the world standard dose, making it easier to obtain an analgesic effect. In the near future, an increase in the use of acetaminophen for pain relief can be expected in Japan. NSAIDs are common drugs for pain in Japan, but often require co-prescription of a gastric mucosal protective agents, H₂- blockers, or proton pump inhibitors(PPI) to prevent gastrointestinal disorders. On the other hand, acetaminophen has much less risk of such adverse reactions and there is no need for co-prescription of digestive medicines. Thus, increased use of acetaminophen could decrease the cost for pain relief in Japan. (Jpn J Pharmacoepidemiol 2012; 17(2): 75-86)

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The spontaneous reporting system for adverse drug reactions(ADRs), through which information is collected on patients who experience ADRs, can lead to hypotheses on causal relationships between drugs and ADRs; however, lack of information on patient characteristics or patients who have not experienced ADRs makes quantitative, relative comparison of risks difficult. From the viewpoint of adapting pharmacoepidemiology to supplement spontaneous reporting of ADRs, RAD-AR Council Japan(RCJ) has been promoting development of a database assembling drug use-results surveillance(DURS) data under the re-examination system for secondary use. RCJ received observational DURS data on antihypertensive drug users from pharmaceutical companies and integrated to develop a database of over 100,000 patients and 19 antihypertensives in 2003. RCJ maintains the database, expanding it to 143,509 patients and 21 antihypertensives in 2007, and also developed a database of antihyperlipidemics with approximately 34,000 patients in 2011. Researchers study these databases through an application and protocol review process stipulated by RCJ, and their results have been presented at conferences and published in articles. This report summarizes DURS data collection and its underpinning regulated systems in terms of data assembly and database maintenance at RCJ. The report also introduces the example for constructing the antihyperlipidemics DURS database and summarizes its patient characteristics. The database is characterized by ADR information and treatment-related laboratory values in addition to patient backgrounds and drug use information. However, it is too small to study rare ADRs and has limited longitudinal observational data. Therefore, RCJ worked to expand the antihypertensives DURS database in 2012 by adding data that include long-term surveillance results. (Jpn J Pharmacoepidemiol 2012; 17(2): 87-97)

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In Japan, large scale health databases were constructed in a few years, such as National health insurance claim and health checkup database(NDB) and Japanese Sentinel project. But the there are some legal issues for making adequate balance between privacy and public benefit by using such databases. NDB is carried based on the act for elderly person's health care but in this act, nothing is mentioned for using this database for general public benefit. Therefore researchers who use this database are forced to pay much concern about anonimization and information security that may disturb the research work itself. Japanese Sentinel project is a National project to detecting drug adverse reaction using large scale distributed clinical databases of large hospitals. Although patients give the future consent for general such purpose for public good, it is still under discussion using insufficiently anonymized data. Generally speaking, researchers of study for public benefit will not infringe patient's privacy, but vague and complex requirements of legislation about personal data protection may disturb the researches. Medical science does not progress without using clinical information, therefore the adequate legislation that is simple and clear for both researchers and patient is strongly required. In Japan, fortunately, the specific act for balancing privacy and public benefit is planned to lay before Diet, but is still under discussion. The author recommended the researchers including the field of pharmacoepidemiology should pay attention to, participate in the discussion of, and make suggestion to this act. (Jpn J Pharmacoepidemiol 2012; 17(2): 101-107)

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In this manuscript, the use of medical information in foreign countries is viewed by taking pharmacoepidemiology studies conducted in US, Sweden and Taiwan as examples. The first example is the cohort study on the association between pioglitazone and bladder cancer using diabetes registry in Kaiser Permanente Northern California(KPNC) which suggested the causal relationship between pioglitazone and bladder cancer. The success of the study was due to the diabetes registry constructed taking long time in KPNC from various data sources including claims data, data of electronic health record and data in pharmacies. The second example is the study on safety of H1N1 vaccine in Sweden. In this study, the vaccine registry was newly developed on the website where almost all of the vaccinated subjects were registered as reimbursement was subject to registration. The web-based registry was linked with the existing common healthcare registers and the investigators estimated hazard ratios of rare outcomes like Bell's palsy and paraesthesia associated with vaccination. The third example is the Large Linked Database(LLDB) to monitor safety of H1N1 vaccination in Taiwan. The LLDB used the technology of IC Card Data Center and the information on diagnosis and vaccination was collected on the daily basis. The risk of various outcomes as in the second study and adverse outcomes associated with pregnancy were monitored. In all of those examples, new mechanisms such as diabetes registry, web-based vaccine registry and the LLDB were established purposefully. The record linkage is the key element to enhance the value of medical information. (Jpn J Pharmacoepidemiol 2012; 17(2): 109-116)

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Japan's national claims database(NDB) was established and its data became available for research purposes. However its potential for research use is considerably limited due to privacy protection requirements and security rules. For example, tabulations containing figures smaller than 10 are not allowed to be published due to the minimal cell size rules. Strangely enough, a similar statistical survey named Health Insurance Claims Survey(HICS) is not subject to such restrictions. Such difference in research use derives from different legal bases: NDB based on the Administrative Personal Data Protection Law while the HICS based on the Statistics Law. The vectors of the two laws are opposite: the Administrative Personal Data Protection Law intends to protect privacy while the Statistics Law intends to enhance data use. Application of the Statistics Law to NDB would be desirable to enhance research use but that would also restrict the government from using NDB data for other purposes such as detection of fraud and abuses. The government has multiple and mutually overlapping statistical surveys on health insurance claims since long before, all of which are subject to the Statistics Law and there is a call for unifying them with a single NDB to avoid duplication and waste. The author proposes, however, that it would be desirable to maintain multiple databases subject to different legal bases to enhance both research use while securing the discretion of the government to use NDB data effectively. Hindrance against effective use of national databases due to legal constraintsfor privacy protection is not limited to Japan. An excerpt of a recent survey results by OECD on national databases and legal restrictions on their secondary use was added for reference. (Jpn J Pharmacoepidemiol 2012; 17(2): 117-134)

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In this summary, we reviewed Japanese large databases available as pharmacoepidemiology data sources. In addition to the National Claims Database, two commercially available insurance claims databases are widely used: Japan Medical Data Center(JMCD) and JammNet.Three large pharmacy claims databases are also reviewed.The pharmacy claims database has unique characteristics in Japan because a prescription is valid only for four days and therefore the prescription records are believed to be almost identical to the dispensing records. Two large hospital-based databases are also available.In order to properly use these databases for the pharmacoepidemiological research questions, we need to learn first the medical practice and medical systems in Japan to have a better understanding for data source and data items. Automated large databases can be a powerful tool for pharmacoepidemiology studies by learning strengths and limitations of each database. (Jpn J Pharmacoepidemiol 2012; 17(2): 135-144)

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Application of a Japanese insurance claims database to pharmacovigilance activities in pharmaceutical industry was discussed. Using a commercially available insurance claims database, incidences of several cancers, the number of patients who were administered anticancer agents, and possible adverse effects were studied. Cancer incidences obtained from the database were virtually equivalent to those from a traditional survey program. The number of cancer patients included in the database with one million beneficiaries, were a few thousands a year. Disorders in epithelial-derived tissue were observed more frequently in lung cancer patients after the initiation of EGF tyrosine kinase inhibitor therapy than after platinum-based therapy, suggesting possible candidates of adverse effects of the EGF tyrosine kinase. We concluded that an estimation of disease incidence and selecting candidates of adverse events with the claims database is theoretically possible. And the database is also applicable to pharmacovigilance fields. (Jpn J Pharmacoepidemiol 2012; 17(2): 145-153)

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Over the last several years, a number of health insurance claims have been electronically submitted and entered into the national database(NDB) by the Ministry of Health, Labor & Welfare(MHLW). A trial was initiated where the NDB would be evaluated for its utility in quality improvement of healthcare services. I had the opportunity to perform the drug utilization study using the NDB, and in this article, I review the procedures by which MHLW make the NDB available and report on issues in analyzing the NDB and in using the NDB for pharmacoepidemiological studies. The NDB is much larger and more encompassing than other medical databases and its findings are expected to havea great influence on a pharmacoepidemiological studies in Japan in providing valuable information on the rational use of drugs. (Jpn J Pharmacoepidemiol 2012; 17(2): 155-162)

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The Diagnosis Procedure Combination(DPC) is a case-mix classification system for hospitalized patients, which is linked with lump-sum payment system called the Diagnosis Procedure Combination/Per-Diem Payment System(DPC/PDPS). The DPC Study Group works on the DPC data utilization project for research purpose, independently of Ministry of Health, Labour and Welfare, Japan. The database contains discharge data and administrative claim data, including diagnoses, comorbidities and complications coded with ICD-10(International Classification of Diseases and Related Health Problems, Tenth Revision) codes; procedures; duration of anesthesia; volume of blood transfusion; drugs and devices used; length of stay; discharge status; costs; and detailed clinical information(body height/weight; smoking index; Japan Coma Scale; cancer stage; modified Rankin Scale; Hugh-Johns classification; NYHA classification for heart failure, severity index for angina pectoris/myocardiac infarction, pneumonia, and acute pancreatitis; and Child-Pugh classification for liver cirrhosis). In this report, we introduced two studies using the DPC database: (i) the effect of fondaparinux on the prophylaxis of postoperative pulmonary embolism and (ii) the effect and cost of gabexate mesylate on the treatment of acute pancreatitis. In addition, we compared the DPC database with the US administrative databases(including the Nationwide Inpatient Sample database and the Medicare claim database) and discussed the tasks for the future set to the DPC database to further enhance clinical studies and health services research in Japan. (Jpn J Pharmacoepidemiol 2012; 17(2): 163-169)

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