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)

STUDY DESIGN: Retrospective case series. PURPOSE: To investigate the oncological outcomes, including distant relapse, after en bloc spondylectomy (EBS) for spinal metastases in patients with a minimum of 2-year follow-up. OVERVIEW OF LITERATURE: Although EBS has been reported to be locally curative and extend survival in select patients with spinal metastases, detailed reports regarding the control of distant relapse after EBS are lacking. METHODS: We conducted a retrospective review of 18 consecutive patients (median age at EBS, 62 years; range, 40–77 years) who underwent EBS for spinal metastases between 1991 and 2015. The primary cancer sites included the kidney (n=7), thyroid (n=4), liver (n=3), and other locations (n=4). Survival rates were estimated using the Kaplan–Meier method, and groups were compared using the log-rank method. RESULTS: The median operative time and intraoperative blood loss were 767.5 minutes and 2,375 g, respectively. Twelve patients (66.7%) experienced perioperative complications. Five patients (27.8%) experienced local recurrence of the tumor at a median of 12.5 months after EBS, four of which had a positive resection margin status. Thirteen patients (72.2%) experienced distant relapse at a median of 21 months after EBS. The estimated median survival period after distant relapse was 20 months (95% confidence interval, 0.71–39.29 months). No association was found between resection margin status and distant relapse. Overall, the 2-year, 5-year, and 10-year survival rates after EBS were 72.2%, 48.8%, and 27.1%, respectively. Importantly, the era in which EBS was performed did not impact the oncological outcomes. CONCLUSIONS: Our results suggest that EBS by itself, even if margin-free, cannot prevent further dissemination, which occurred in >70% of patients at a median of 21 months after EBS. These results should be considered and conveyed to patients for clinical decision-making.
Clinical Decision-Making ; Follow-Up Studies ; Humans ; Kidney ; Liver ; Methods ; Neoplasm Metastasis ; Operative Time ; Recurrence ; Retrospective Studies ; Spine ; Survival Rate ; Thyroid Gland

BACKGROUND/AIMS: The aim of this study was to examine the convenience of the quality of life and utility evaluation survey technology (QUEST) questionnaire and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire as self-assessment diagnostic instrument. METHODS: This was a two-way crossover study conducted over 6 weeks from September 2010 to November 2010. The subjects were 60 consecutive patients admitted to the Hiratsuka city hospital with a gastrointestinal condition, regardless of the coexistence of heartburn. They were assigned to fill in both the QUEST and FSSG questionnaires in random order. We analyzed the time taken to complete the questionnaires, whether subjects asked any questions as they filled in the questionnaire, and the questionnaire scores. RESULTS: Comparison of the QUEST and the FSSG revealed significant differences in the completion time (196.5 vs. 97.5 seconds, respectively; P < 0.0001) and in whether subjects asked any questions (37 vs. 15 subjects, respectively; P < 0.0001). Completion time in QUEST scores of > or = 4 was lower than < 4 (170.5 vs. 214.0 seconds, respectively; P = 0.022), and the QUEST score was significantly higher without questions than with question (3 vs. 1 points, respectively; P = 0.025). CONCLUSIONS: This study revealed that the FSSG questionnaire may be easier for Japanese subjects to complete than the QUEST questionnaire.
Asian Continental Ancestry Group ; Cross-Over Studies ; Gastroesophageal Reflux ; Heartburn ; Hospitals, Urban ; Humans ; Quality of Life ; Surveys and Questionnaires ; Self-Assessment