Makoto Shiragami

Contribution of antimicrobial stewardship programs to reduction of antimicrobial therapy costs in community hospital with 429 Beds --before-after comparative two-year trial in Japan

ObjectivesDo antimicrobial stewardship programs (ASPs) contribute to reduction of antimicrobial therapy costs in Japanese community hospitals? To answer this health economic question, a before-after comparative two-year trial in a community hospital in the country was designed.MethodsThe study was conducted at National Hospital Organization Tochigi Medical Center, a community hospital with 429 beds. We compared six-month period before-ASP (January 2010 to June 2010) and 24-month period after ASP (July 2010 to June 2012) in primary and secondary outcome measures. Three medical doctors, three pharmacists and two microbiology technologists participate in the ASPs. The team then provided recommendations based on the supplemental elements to primary physicians who prescribed injectable antimicrobials. Prospective audit with intervention and feedback was applied in the core strategy while dose optimization, de-escalation and recommendations for alternate agents and blood cultures were applied in the supplemental elements. The primary outcome was measured by the antimicrobial therapy costs (USD per 1,000 patient-days), while the secondary outcomes included the amount of antimicrobials used (defined daily doses per 1,000 patient-days), sensitivity rates (%) of Pseudomonas aeruginosa (P. aeruginosa) to Meropenem (MEPM), Ciprofloxacin (CPFX) and Amikacin (AMK), length of stay (days) and detection rates (per 1,000 patient-day) of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase-producing organisms (ESBLs) through blood cultures.ResultsIn the study, recommendations were made for 465 cases out of 1,427 cases subject to the core strategy, and recommendations for 251 cases (54.0%) were accepted. After ASP, the antimicrobial therapy costs decreased by 25.8% (P = 0.005) from those before ASP. Among the secondary outcomes, significant changes were observed in the amount of aminoglycosides used, which decreased by 80.0% (P < 0.001) and the detection rate of MRSA, which decreased by 48.3% (P < 0.001).ConclusionsThe study suggested the possibility that ASPs contributed to the reduction of the antimicrobial therapy costs in a community hospital with 429 beds.

DEVELOPMENT OF ORPHAN DRUGS IN JAPAN: CHARACTERISTICS OF ORPHAN DRUGS DEVELOPED IN JAPAN*

Since 1993, some support measures to promote development of orphan drugs have been introduced. This support system was modeled after the United States system, but the contents were slightly different. The annual average numbers of orphan drug designations in Japan is about one half of those in the United States. The proportion of approved orphan drugs to designated drugs in Japan was 2.0 times of that in the United States. In the United States, 77% of applicants were smaller companies, but in Japan only 3% of applicants were venture companies. In Japan more drugs were introduced from overseas than developed in the country. Looking at the designated orphan drugs, drugs with less chance of failure which required less money for development tend to have been developed in Japan. Most of the applicants were larger companies. It seems important to view the support measures from the point of view of fostering venture companies.

Development of Orphan Drugs in Japan: Effects of a Support System for Development of Orphan Drugs in Japan*

In order to promote development of orphan drugs, the Japanese Ministry of Health and Welfare introduced support measures for drug development in 1985 and 1993. To see if these support measures were really effective for drug development, we compared the number of orphan drugs and review periods required for their approval in three different periods. The number of approved drugs in a year of Term 3 (after 1993) was approximately 3.3 times that of Term 1 (before 1985). The median value of the review period required for approval of drugs in Term 3 was 15.5 months, shorter than that in Term 1 by 10.5 months. It was clearly shown that the number of drugs developed was increased and the review period was significantly reduced because of the support measures. Now it is possible for patients suffering from orphan diseases to get access to new and more effective drugs sooner.

Valuing the Drug Information Provided for Generics in Setting the Price of Generic Drugs in Japan

The recent tightening of financial resources for medical services in Japan sets the stage for continued expansion of the use of generic drugs. However, safety and efficacy, as well as cost, must be taken into account in any evaluation of a generic drug. In this study, the drug information provided for therapeutically-equivalent drugs was compared to that for the brand-name product as a means of evaluating the generic versions of the drug. Drug information was evaluated by means of a quantitative analysis of information included in package inserts and “interview forms” (product information sheets). Information per price unit was also calculated. Finally, the ratio of information on generic drugs to information on brand-name drugs (Qua) was calculated. This method was chosen because although the price of pharmaceuticals is regulated in Japan, some brand pharmaceutical manufacturers hold that the prices of drugs are a reflection of the quantity of information provided. We sought, therefore, to compare quantity of information per unit price. By drug formulation, the Qua ranged from 0.47 ±0.51 to 1.26 ±0.57 (mean±SD). By pharmaceutical manufacturer, the Qua ranged from 0.20 ± 0.50 to 1.48 ± 0.29 (mean ± SD). It can be concluded that less information is provided for generic drugs than for brand drugs, but the difference in the quantity of information is based on differences in manufacturer policy in provision of information. It then becomes clear that if drug information is to be considered a valuable component of a pharmaceutical product that should figure into the price of that product, there are products that do not present information in line with the current pricing policy.

喘息の治療と管理におけるサルメテロール／フルチカゾン製剤の費用対効果 —プロピオン酸フルチカゾンとの比較検討—

We commenced to estimate the economic impact of salmeterol/fluticasone combination (SFC) therapy compared to fluticasone propionate (FP) therapy for asthma control in Japanese patients. A Markov model with five health states, developed by Price in 2002, was used. 1-week transition probabilities among status of asthma management were obtained from literature and epidemiological data from public data base. Direct cost for treatment was estimated from Japan medical fee schedule. Cost and effectiveness were not discounted due to 12-week simulation by the model. Univariate sensitivity analyses were undertaken to examine the main variables affecting cost-effectiveness. Probabilistic analysis was also undertaken to discuss statistical argument and to provide information for decision-making. In this analysis, the model was run over a 12-week period of time using transition probabilities. The results showed that treatment with SFC resulted in a higher proportion of totally controlled weeks per patient than treatment with FP (65.0 vs. 49.5%; incremental effectiveness by 15.5%), and lower mean direct asthma management costs ( yen168 702 vs. yen227 820). Probabilistic sensitivity analysis, conducted to assess robustness of the above base case result, showed that in the 95% of cases SFC was dominant (more effective and less costly) to FP. It suggested that SFC will be the most cost-effective therapy for asthma control. It would, however, be required to further evaluate cost-effectiveness of SFC in long-term observation.

Greeting and General Statement by the Organizer

Regulatory science is growing increasingly important, and the Health and Medical Strategy of the Japanese government reflects this. How regulatory science is covered in pharmaceutical education is an urgent issue. Education on regulatory science is also part of the modified version of the model core curriculum in the six-year pharmaceutical course that was introduced from 2015. The Regulatory Science Task Force of the Pharmaceutical Society of Japan, in response to a commission of the Ministry of Education, Culture, Sports, Science and Technology, conducted a study on the development of teaching material and educational methods for regulatory science, held a symposium with the participation of pharmaceutical educators in February 2015, and proposed draft teaching material based on the discussions during the symposium. The draft consists of two parts. Part one consists of a general statement on the purpose and definition of regulatory science and explanations of regulatory science with examples in various fields. Part two proposes case methods for participatory education. As the draft was developed in a limited time by a limited number of people, some issues remain to be resolved, such as few pharmacist-related examples for explanation and scenarios for case methods are included. Experts from various fields will make proposals for improving the teaching material, and educators will report on the status of regulatory science education. These issues will then be discussed with the audience. The organizers hope that the symposium will provide an opportunity to deepen our understanding of regulatory science and enhance education in it.