Introduction : Meta-analysis is well recognized as the most important study methodology in pharmacoepidemiology. The cause of heterogeneity of the effects among studies in the conventional meta-analyses, has been typically analyzed by meta-regression and sometimes by extracting several studies in a post hoc manner, constructing subgroups from these studies and analyzing the effect in this subgroup. However, if multiple study subgroups are produced in a post hoc manner, since the potential possible number of subgroups is very huge, the multiplicity of testing results in the inflation of the type I error rate. Therefore, even when a significant subgroup has been identified, it can represent a type I error, due to multiplicity of testing. To insist on the significance of a post hoc subgroup analysis, it is indispensable to conduct an analysis adjusted for multiplicity.
Objective : The present study was undertaken to establish a method for resolving the problem for the multiplicity of subgroup analysis in meta-analysis.
Methods : Performance comparisons among the Bonferroni method, the Holm method, the Scheffe type method and the closed testing procedure were conducted, assuming the actual meta-analysis of clinical studies on colon cancer.
Results : In the subgroup analysis without adjustment for multiplicity, the probability of type I error was unacceptably high. On the other hand, the four methods mentioned above can control this probability to below the nominal significance level. Under many situations, the closed testing procedure showed a relatively higher power, and this method was particularly superior to the other methods when a relatively high percentage of studies revealed minor effects.

Objective:The aim of this study was to measure the value of over-the-counter (OTC) pravastatin as a healthcare-related item by investigating the public's willingness to pay(WTP)in self-medication for the primary prevention of myocardial infarction (MI)if pravastatin were switched to OTC status.
Methods:A questionnaire survey was distributed among those receiving health checkups at Kitasato Institute Hospital. For the WTP question format, the double-bound dichotomous choice approach was employed. Participants were randomly assigned to three groups. Group A was provided with a starting price per month of \5,000, group B with \8,000, and group C with \12,000. To investigate factors affecting WTP, Weibull regression analysis was used.
Results:The questionnaire survey was completed by 242 individuals(150 men, age range 30-82 years), and the mean WTP was \9,583 per month. Weibull regression analysis showed that age significantly affected WTP. The monthly cost for a physician consultation to receive prescribed pravastatin is \3,540 to \6,590 in the Japanese health insurance system.
Conclusion:The WTP was about \10,000 per month, and the WTP based on the questionnaire responses was more than two-fold higher than the present cost for a physician visit. This study clarified the WTP if pravastatin for the primary prevention of MI were switched to OTC status. Further studies are necessary to elucidate whether this would contribute to the promotion of self-medication among Japanese.

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.

Objective: In Japan, beta 2 agonist (BA) has an indication for acute bronchitis with airway obstruction. To investigate BA prescribing practices for children whose diagnosis were acute bronchitis without asthma in Japan, a database study and interviews with pediatricians were conducted.
Design: Database study
Methods: We conducted a database study. Using the Japan Medical Data Center database, medical receipts of about 100,000 children younger than 18 years old were obtained between 2005 and 2008. First we identified all the new incidences (362,287 cases) of upper respiratory tract infection, influenza, or acute bronchitis. Outcome measure was prescription of BA within 21 days of the incidence. We calculated the prescription proportions of BA for the asthma group (41,064 cases) and the non-asthma group (321,223 cases). We then interviewed 10 pediatricians to elucidate the reason why they prescribe BA for patients.
Results: The proportion of children prescribed BA at least once a year in 3-5 years old was 49.9 %. Among 3-5 year olds with acute bronchitis, the BA prescription proportions in the asthma group (58.6%) was nearly as high as that in the non-asthma group (56.6%). Although BA prescription proportions in the asthma group decreased annually with the exception of 0-2 years old, those in the non-asthma group remain unchanged. Based on the interview study, we found interpretations of airway obstruction for acute bronchitis without asthma were broadly-divided into 2 types: the effect of inducing bronchospasm and the effect of producing large amounts of secretions in the airways.
Conclusion: In this study, it was revealed that pediatric patients with acute bronchitis were commonly prescribed BA in Japan. To promote an appropriate use of BA, prescriptions of BA to non-asthma pediatric patients should be carefully watched. (Jpn J Pharmacoepidemiol 2012; 17(1): 1-12)