Although the recent revision of the ministerial ordinance on Good Post-marketing Study Practice (GPSP) included the utilization of medical information databases for post-marketing surveillance, there has been limited research on the validity of diagnosis codes and other outcome definitions in Japanese databases such as administrative claims (“receipt”) database. This task force proposed how to conduct good validations studies, based on the narrative review on around 100 published papers around the world. The established check list consists of ： (ⅰ) understanding the type of the database (e.g. administrative claims data, electronic health records, disease registry) ； (ii) understanding the setting of the validation study (e.g. “population-based” or not) ； (iii) defining the study outcome ； (iv) determining the way of linkage between databases ； (v) defining the gold standard ； (vi) selecting the sampling method (e.g. using the information of all patients in the database or a hospital, random sampling from all patients, random sampling from patients satisfying the outcome definition, random sampling from patients satisfying and not satisfying the outcome definition, “all possible cases” method) and sample size ； (vii) calculating the measures of validity (e.g. sensitivity, specificity, positive predictive value, negative predictive value) ； and (viii) discussing how to use the result for future studies. In current Japan, where the linkage between databases is logistically and legally difficult, most validation studies would to be conducted on a hospital basis. In such a situation, detailed description of hospital and patient characteristics is important to discuss the generalizability of the validation study result to the entire database. This report is expected to encourage and help to conduct appropriate validation studies.

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.

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.

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.

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)