The utilization of medical information is a pressing issue for pharmaceutical companies, particularly from the perspective of pharmacovigilance applications. There are currently some types of adverse reaction risks that cannot be detected in Japan but can be detected in Europe and the U.S.A. because secondary use of medical information is possible there. To remedy this lag, it is essential that we update the framework of Japan's system. We must create medical information standards that allow public use and we must define a level of quality control.

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)

The reform of regulation is proposed to implement the Pharmacovigilance Planning (PVP) based on the ICH E2E guidelines as indicated in the notification of Risk Management Plan (J-RMP). Even after the J-RMP is enforced, the pharmacovigilance method still heavily depends on the traditional methods like “drug use results surveys”. The “Good Post-marketing Study Practice (GPSP)” ordinance and related notifications are the root causes of the malfunctioned operation of the system. Specifically, 1) the GPSP ordinance does not encourage the investigations according to the ICH E2E notification and 2) it is believed that the pharmacovigilance method should be limited to one of the three options only, namely, “drug use results surveys”, “specific use surveys” and “post-marketing clinical studies”. The followings are proposed:
• The GPSP ordinance should be revised to encourage referring the annex “pharmacovigilance methods” in “Pharmacovigilance planning”.
• The use of the early post-marketing phase vigilance (EPPV) should be restricted to the drugs marketed at the same time in the world or marketed for the first time in Japan.
• The notification connecting the “Good Vigilance Practice (GVP)” and GPSP ordinances (March 11, 2013, No 0311-7) should be revised to include a prescription that the “Safety Control Manager encourage the Post-marketing Surveillance Control Manager to develop a pharmacovigilance plan according to the ICH-E2E guidelines”.
• Forms attached to the individual RMP submissions should be revised according to the J-RMP notification.
• The notification on the RMP development (No.0426-1 and No.0426-2, on April 26, 2012) should be revised to indicate that the study design is acceptable to the health professionals.
• It should be clarified that the additional pharmacovigilance activities may be conducted by the divisional cooperation in the world or may be conducted as a non-clinical study, if appropriate.

Those of us in the pharmaceutical industry are in favor of using SS-MIX standardized storage to alleviate the burden on medical professionals. As previously suggested, in addition to the benefits of reducing study periods, supporting a variety of investigative research and safety measures, and obtaining more accurate data on disease states and treatments, actively using this kind of new technology is a societal imperative in an information-driven society. Possible practical uses include (1) general application in drug use surveillance and special drug use surveillance, (2) appropriate sampling surveys, (3) patient monitoring, (4) observational studies with controls, such as those using disease registries, and (5) reviewing the results of safety measures. However, there is the issue of regulatory interpretation and consensus, with debate on information protection, and the issue of social infrastructure. Therefore, industry, government, and academia must continue its active, cooperative discussion to enable true implementation of this technology. (Jpn J Clin Pharmacoepidemiol 2013; 18(1): 57-64)

A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.
1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities
2．How to select Safety Specification (SS) and describe its characteristics
・Selection of SS
・Characterization of SS
・Association with Research Questions (RQ)
3．How to define and describe RQ
・What is RQ ?
・RQ interpretation in other relevant guidelines
・Methodology to develop RQ for PVP with examples
・Best approach to integrating PVP for whole aspects of safety concern
4．How to optimize PVP for specific RQ
・Routine PVP or additional PVP ?
・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)
・Checklist to help develop PVP
5．Epilogue:
・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.
・Significance of background incidence rate and needs for comparator group
・Infrastructure for the future PVP activities
6．Appendix: Checklist to help develop PVP activities in RMP
The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.

The Standardized Structured Medical record Information eXchange (SS-MIX) was started in 2006 as the project supported by the Ministry of Health, Labour and Welfare (MHLW) for promoting the exchange of the standardized medical information. Free soft wares developed in the project allow the storage of medical information to receive HL7 messages for prescription, laboratory test results, diagnoses and patient demographics in the hospital information system (HIS). We encourage the use of the SS-MIX standardized storage for postmarketing surveys and clinical studies. The recommendations consist of the following 7 parts. [1] In surveys and clinical studies, the information of drugs and laboratory test results in the SS-MIX standardized storage can be directly transferred to the electronic questionnaire and the investigators may obtain the information with high accuracy and granularity. [2] The SS-MIX standardized storage works as the backup system for the HIS because it can provide the minimum information essential in patient care even under the disastrous condition like earthquake or unexpected network failure. [3] The SS-MIX standardized storage may be useful to conduct a good pharmacoepidemiology study not only because it provides the information in the storage efficiently but also it can be used to identify “new users” who started the drug after some period of non-use.The “new user” design is often essential to have the unbiased results. [4] When the drug company conducts postmarketing surveys according to the current regulation, the use of the SS-MIX standardized storage will facilitate the fast and efficient collection of data to develop the timely measure to minimize the drug-related risk. With the SS-MIX standardized storage, it is also expected that many types of study design can be employed and the quality of data is improved in the survey. [5] The SS-MIX standardized storage maybe also useful to evaluate the risk minimization action plan by comparing the prescription pattern or incidence of the targeted adverse event between two periods before and after the implementation of the action plan. [6] In planning clinical trials, the SS-MIX standardized storage may be used to estimate the size of eligible patients. The storage may also allow conducting cross-sectional studies to know characteristics of diseases or drug treatment. In addition, cohorts of those who had coronary artery angiography, new users of a drug and those with a rare disease may be readily identified. Using such cohorts, investigators can initiate a case-control study nested within the cohort, pharmacogenomic studies and comparative effectiveness researches. [7] The SS-MIX standardized storage may be used as the formal data source in clinical trials in the future when some conditions are satisfied. For instance, the formal agreement should be reached between industry, government and academia on the use of standards of data structure in Clinical Data Interchange Standards Consortium (CDISC) and on the operation of computerized system validation (CSV) in the clinical trials.