Objective: To explore the data sources used in economic evaluations performed on new drugs, and to propose an improved data infrastructure in Japan.
Design: A systematic review.
Methods: We systematically reviewed economic evaluation studies of the new drugs which were launched in Japan between April 2006 and March 2011, and have been priced by the cost calculation method. The “Ichushi” and Pubmed databases were used to find the published articles.
Results: 198 drugs were priced under cost calculation methods in the last 5 years in Japan. 14 published articles (9 drugs) were found: 5 CUAs and 10 CEAs (including one that was both CUA and CEA). In all studies, several data from different sources were incorporated. Cost data were estimated by using standard treatment protocols and national price lists for drugs and medical services, or obtained from limited number of claims data. Efficacy data were obtained from RCTs or clinical trial data mostly conducted in Japan. In 4 out of the 5 CUAs, utility data were used from other studies conducted on non-Japanese samples. Other data, such as epidemiological data, were adopted from overseas as well as Japanese studies.
Conclusion: In order to increase quality and efficiency to conduct economic evaluations in Japan, three steps need to be taken in the data environment: increased accessibility to large cost databases such as the national claims database; establish an epidemiological database; and collect and accumulate utility data in Japanese samples.

One of the target points in the PMDA 2nd midterm plan (FY2009-2013) is reinforcement and enhancement of the system for safety evaluation for pharmaceuticals using expanded data sources beyond spontaneous reports of adverse drug reactions (ADRs). To achieve this goal, PMDA started investigation in FY2009 to develop methodology to utilize electronic medical information for secondary purpose of safety evaluation of pharmaceuticals. (MIHARI project- Medical Information for Risk Assessment Initiative)
Data sources targeted in MIHARI project are claims data, diagnosis procedure combination (DPC) data, hospital information system (HIS) data, etc.
Secondary use of electronic medical information for safety evaluation is expected to enable safety evaluation based on quantitative analysis, which has been difficult so far. It will also provide faster and easier way of evaluation compared to collecting primary data from study planned and conducted just for the purpose.
PMDA intends to establish the system to utilize electronic medical information (eg. claim data, DPC data, HIS data) practically for safety evaluation by the end of FY2013. Aiming for this, PMDA is conducting various pilot studies using currently available data in the MIHARI project. Here we report on recent developments of this project.

PMDA started MIHARI project in FY2009 to enhance drug safety assessment by developing ways to utilize electronic medical information as additional data sources to spontaneous adverse drug reaction reports. The project has been established according to PMDA's second midterm plan. In this article, we will introduce latest two studies (pilot studies No. 4 and 5) using data of standardized electronic medical record(EMR) called SS-MIX (standardized structured medical record information exchange) data out of our several pilot studies. SS-MIX is a standard specification published by the Ministry of Health, Labour and Welfare. In these studies, anonymized SS-MIX data were provided by six collaborative hospitals respectively. In pilot study No. 4, we explored approaches for evaluating the impact of regulatory action which instructed relevant manufacturers to revise package inserts of sitagliptin phosphate hydrate (sitagliptin) to call physician's attention. The revision was about reducing dose of sulfonylurea (SU) to avoid serious hypoglycemia when it is prescribed concomitantly with sitagliptin. As indicators of the impact, we evaluated changes in proportion of concomitant use and average SU dose before and after the action and estimated the risk of hypoglycemia in concomitant users compared to SU alone users before and after the action. In conclusion, evaluating impact of the regulatory action using SS-MIX data was technically feasible; however, it was difficult to analyze with adequate accuracy due to limited size of the data. In pilot study No. 5, we examined validity of outcome definitions for hyperthyroidism which were applied to combinations of some data elements of SS-MIX data to identify the patients. Three types of outcome definitions were prepared; 1) definitive diagnosis of hyperthyroidism, 2) prescription of medication for hyperthyroidism, 3) prescription of medication for hyperthyroidism in or after the month in which definitive diagnosis of hyperthyroidism was given. Criteria for case ascertainment were determined according to relevant clinical guidelines. After the cases were ascertained, positive predictives values were calculated. The results suggested that using information on prescription of medication improves validity of definition of outcome. The findings from pilot studies in MIHARI project have been utilized in another project which PMDA is carrying forward now (EMR network project). The findings would be also helpful when we use data from this network. (Jpn J Pharmacoepidemiol 2013；18(1)：23-29)

Objective: We conducted a questionnaire survey to comprehend the situation regarding the collection, provision, and utilization of drug safety information at hospitals.  In addition, we asked pharmaceutical companies how they select medical institutions to provide drug safety information.  We also investigated the current situation of information provision to Tokyo Medial Center by pharmaceutical companies.
Method: A questionnaire was mailed to all hospitals in Japan.  The survey was conducted between January 13 and February 10, 2011.  Moreover, we asked thirteen pharmaceutical companies by telephone and e-mail about the implementation status of the provision of information and performed a survey at Tokyo Medical Center on the current situation of information provision by pharmaceutical companies regarding revisions to precaution sections in package inserts.
Results: The results of the questionnaire survey (response rate: 41.2%) showed that the major information sources for hospitals were medical representatives (77.8%), Drug Safety Update (50.3%) and direct mails (49.3%).  Furthermore, in the case of drugs prescribed exclusively for extramural dispensing, fewer hospitals responded that medical representatives of the pharmaceutical companies provided drug safety information and more hospitals responded that they did not obtain any drug safety information at all, compared with drugs listed in the hospital formularies.
Conclusion: To minimize the risks of drugs, healthcare professionals must collect a wide range of drug safety information and must utilize this information in their medical practice.  Therefore, it is important that pharmaceutical companies and regulatory authorities make an effort to provide suitable information dissemination to medical institutions.  Furthermore, medical institutions must also strengthen their systems for collecting drug safety information and providing such information to healthcare professionals.

OBJECTIVE: This study estimated the effects of weekend and off-hour childbirth and the size of perinatal medical care center on the incidence of cerebral palsy. METHODS: The cases were all children with severe cerebral palsy born in Japan from 2009 to 2012 whose data were stored at the Japan Obstetric Compensation System for Cerebral Palsy database, a nationally representative database. The inclusion criteria were the following: neonates born between January 2009 and December 2012 who had a birth weight of at least 2000 g and gestational age of at least 33 weeks and who had severe disability resulting from cerebral palsy independent of congenital causes or factors during the neonatal period or thereafter. Study participants were restricted to singletons and controls without report of death, scheduled cesarean section, or ambulance transportation. The controls were newborns, randomly selected by year and type of delivery (normal spontaneous delivery without cesarean section and emergency cesarean section) using a 1:10 case to control ratio sampled from the nationwide Japan Society of Obstetrics and Gynecology database. RESULTS: A total of 90 cerebral palsy cases and 900 controls having normal spontaneous delivery without cesarean section were selected, as were 92 cerebral palsy cases and 920 controls with emergent cesarean section. A significantly higher risk for cerebral palsy was found among cases that underwent emergent cesarean section on weekends (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.06-2.81) and during the night shift (OR 2.29, 95% CI 1.30-4.02). No significant risk was found among normal spontaneous deliveries on weekends (OR 1.63, 95% CI 0.97-2.73) or during the quasi-night shift (OR 1.26, 95% CI 0.70-2.27). Regional perinatal care centers showed significantly higher risk for cerebral palsy in both emergent cesarean section (OR 2.35, 95% CI 1.47-3.77) and normal spontaneous delivery (OR 2.92, 95% CI 1.76-4.84). CONCLUSION Labor on weekends, during the night shift, and at regional perinatal medical care centers was associated with significantly elevated risk for cerebral palsy in emergency cesarean section.
Case-Control Studies ; Cerebral Palsy ; epidemiology ; etiology ; Delivery, Obstetric ; statistics & numerical data ; Health Facilities ; statistics & numerical data ; Humans ; Incidence ; Infant, Newborn ; Japan ; epidemiology ; Parturition ; Perinatal Care ; statistics & numerical data ; Retrospective Studies ; Time Factors