The current conditions of the medical system and the health insurance system in Japan and situations in other countries indicate that pharmacoeconomics will become indispensable for pharmacists. In the model core curriculum issued by the Pharmaceutical Society of Japan in August 2002 pharmacoeconomics is a special field of pharmaceutical science to be taught at colleges. However, most instructors at colleges of pharmaceutical science are unfamiliar with pharmacoeconomics. I shall describe efforts to introduce pharmacoeconomics into the curriculum for pharmaceutical science. Because some instructors opposed a class devoted to pharmacoeconomics, I started to teach pharmacoeconomics as a part of an existing class. Considerable effort will be required to establish a required class devoted to pharmacoeconomics.

Objective: It is very difficult to identify the frequency of rare adverse drug reactions (ADRs) precisely.  A study was conducted to estimate the frequency of ADRs that were not observed in clinical studies by referring to the sales volume of the pharmaceuticals until the date when the ADR was first observed after a drug was marketed.
Methods and Subjects: The study was conducted for the 17 pharmaceuticals to estimate the frequency of Hepatopathy.  The date of report of the ADR to the Minister was obtained through information disclosure requests.  The sales volume of the relevant pharmaceuticals was provided by IMS Japan.  On the premise that all the ADRs were detectable, the probability (P) that an ADR was not detected right before drug administration in the first case of the ADR was estimated through Formula 1.
Formula 1 : P=1−{(D₀−S)!÷(D₀−S−D_N)!}/{D₀!÷(D₀−D_N)!} = 1−{(D₀−D₀×F)!÷(D₀−D₀×F−D_N)!}/{D₀!÷(D₀−D_N)!}
  D₀ referred to the estimated person-days for all the patients subject to the drug therapy, S to the number of patients with ADR, D_N to the person-days until the date when the ADR was observed and F to the frequency of the ADR.  F was estimated where the detection P was 0.95 or was close to 0.95.
Results and Discussion: Among the pharmaceuticals investigated, the frequency was highest in product A (0.038%) and was lowest in product X (0.0000088%).  In many cases, the package inserts describe the frequencies of rare ADRs as unknown.  However, the frequency can be estimated relatively precisely through the method stated above using data, which may be kept by pharmaceutical manufacturers.

Objective: Currently, post marketing surveillance (PMS) for prescription-only to over-the-counter (OTC) switched products is conducted based on questionnaires to patients.  These questionnaires appear in the form of postcards and are completed and posted voluntarily by patients.  With such a method, however, it is not possible to select samples randomly and there may be a bias in respondents.  In addition, the response rate of questionnaire postcards tends to be low.  It is not really credible that the efficacy and safety of OTC switches are confirmed by such a method.  An investigation was therefore conducted with the aim of developing an effective method of PMS for OTC switches in order to achieve the intended objective of PMS.
Method and Subjects: Famotidine purchasers were asked to complete a questionnaire form.  The pharmacists asked the subjects to complete the questionnaire form again on their second visit and also checked patient compliance with drug treatment.  The effectiveness of this method was evaluated by reviewing responses to the questionnaire on the first and second visits.
Results and Discussion: It was suggested that the method tested in this investigation may possibly facilitate evaluation of the efficacy of OTC switched products, detection of adverse drug reactions and monitoring of patient compliance with drug treatment.  However, the questionnaire used in the investigation was not suited for detecting symptoms that triggered patients to purchase famotidine.  It was considered necessary to prepare additional questions specifically designed to detect such symptoms.

[Objectives] It has been demonstrated that HMG-CoA reductase inhibitors (statins) effectively reduce the low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels in the blood, and currently, statins are most widely used for the treatment of hyperlipidemia.  On the other hand, it has been demonstrated that fibrates more effectively reduce the blood triglyceride level (TG).  However, concomitant use of statins and fibrates is contraindicated.
  Therefore, practical and situational use of fenofibrate (fibrate therapy) and atorvastatin (statin therapy) was investigated in patients with high TG and LDL-C levels in consideration of cost effectiveness.
[Method] Baseline TG and LDL-C levels were stratified, and a table of combination was prepared for TG and LDL-C values.  Effectiveness was measured by the number of patients who were able to achieve treatment targets.  Treatment targets were set referring to the reduction rate of serum lipid levels in dose finding studies of fenofibrate and atorvastatin and the target lipid levels identified in 2007 Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases.  Costs were measured by annual drug treatment costs, and the incremental cost effectiveness ratio of atorvastatin to fenofibrate was then estimated.  According to the actual patient distribution, the incremental cost effectiveness ratio of atorvastatin to fenofibrate in patients with TG level over 150 mg and LDL level over 140 mg was also estimated.
[Results] Fenofibrate was dominant over atorvastatin where effectiveness was higher and costs were lower in fenofibrate treatment in two patient groups; patients with LDL-C level under 160 mg patients with TG level over 170 mg and LDL-C level between 160 mg and 170 mg patients with TG level over 190 mg and LDL-C level between 170 mg and 180 mg patients with TG level over 230 mg and LDL-C level between 180 mg and 190 mg patients with TG level over 250 mg and LDL-C level between 190 mg and 200 mg patients with TG level over 290 mg and LDL-C level between 200 mg and 210 mg patients with TG level over 350 mg and LDL-C level over 210 mg.  In an analysis made according to the actual patient distribution, 571 fenofibrate patients and 534 atorvastatin patients were able to achieve the treatment targets, and fenofibrate was dominant over atorvastatin where effectiveness was higher and costs were lower in fenofibrate treatment.

[Purpose]
The purpose of this study was to demonstrate the effectiveness of Kampo medicines, from the aspect of cost effectiveness. We obtained judgment criteria by analyzing past published papers and implemented our study according to criteria about the kinds of formulations and diseases that were suitable for pharmacoeconomic analysis.
[Method]
First, we extracted the original, clinical, and NHI price listed formulations (EA) from each published paper, by searching for Japanese key words such as “_??__??_ (Kampo)” or “_??__??_ (economic)” in the databases of “Igaku Chuo Zasshi” and “Institute for Health Economics and Policy.” Considering the importance establishing a controlled treatment method in pharmacoeconomic analysis, we defined papers with a comparative control (Comp) as one judgment criterion (1), then extracted these data; and analyzed how target (diseases and formulations), controlled formulation, measurement outcomes, and “Sho” (patterns or syndromes) were handled in each paper. Secondly, we defined those formulations which had been referred to many times in the EA as our second judgment criterion (2), because we thought they had abundant and clear outcomes, and then implemented an outcome analysis of them.
[Results and Discussion]
Judgment criterion (1): The number of formulations, and the total number of papers referring to a Comp (38 articles) were 25 and 41 (Shoseiryuto [4], Shosaikoto [4], Kyukichoketsuin [3] in descending order) respectively. Approximately two-thirds of target illnesses covered in these papers were gastrointestinal diseases, infectious diseases, ear nose and throat diseases; and in women, pregnancy or delivery-related diseases. Concerning outcomes, only 10.5% of the papers measured human outcomes such as quality of life (QOL), which might suggest that the implementation of cost effectiveness analysis was difficult. The results of analyzing how to handle “Sho” suggested that Kyo-sho or Vacuity-sho patient formulations tended to exert their treatment effects relatively, even without consideration for “Sho”.
Judgment criterion (2): Using EA prices, we expedientially defined frequently referred formulations as those referred to in 15 or more of the total research paper number, and then extracted them. As the result of this extraction, 6 formulations (Hochuekkito, Keishibukuryogan, Shishihakuhito, and etc.) were obtained. Among these formulations, Shishihakuhito had high rates (88.2%) for achieving treatment goals, including the improvement of skin symptoms such as erythema and pruritus.
[In Conclusion]
A comparison between Kampo and Western medicines was not simply applicable, due to large differences between their mechanisms of action, and the ways they exert their effect, even if their ultimate effects are the same. We would need to create a study plan which would cover human outcomes when making a further pharmacoeconomic study, because Kampo medicines do have a good chance of improving QOL. We would even say that Vacuity-sho formulations given to patients could easily work, without consideration for “Sho”.

[Purposes] Evidence-based medicine (EBM) is now the established standard for selecting appropriate treatment, the basic ideas of which cannot be ignored even in the field of Kampo medicines. With this in mind, we conducted a meta-analysis (MA) for those Kampo medicines which had been administered in randomized clinical trials, as a method of establishing the evidence for Kampo medicines, and then examined the resulting data obtained for the present study. Here, we focused on the assessing the usefulness in postpartum control, using Kyukichoketsuin (KCI), with methylergometrine maleate (MME) as control.
[Methods] We searched and collected articles published before September 2004 in Igaku Chuo Zasshi (Japana Centra Revuno Medicina) and Medline using keywords such as “Kyukichoketsuin”, etc. First we selected target articles for analysis in accordance with our inclusion criteria and examined the quality of those articles using a score system adopted by Chalmers, in 1981. Then we extracted target data from the articles in accordance with meta-analytic methods, integrated the resulting data using the DerSimonian-Laird method, and implemented sensitivity analysis to them.
[Results and Discussion] We selected four articles for our target analysis. All four were of similar quality. When we set post-labor pains as an assessment item, and integrated three of the four articles, KCI showed that it more significantly decreased those pains compared to MME, with an integrated odds ratio of 0.32 (95%CI, 0.17-0.60). The one remaining independent article, however, in which KCI exerted statistically significant effect in height of day-five uterine fundus, indicated no higher significance through integration with the first three articles. Also, even integrating the height of the uterine fundus shown in the articles, on day four as well as the height before integration, had no significance. These results indicate that the effect of KCI for the involution of the uterus may be the same as that of MME. Regarding the volume of breast-milk lactation on day four in comparison between two test drugs, some articles showed more volume in both the KCI and MME. groups, despite reaching no significant decreases in volume, with an integrated odds ratio of -8.20 (95%CI, -16.17--0.23). However, contrary to this, results for the integration of day-five breast-milk lactation volume showed an increase in the KCI group, although without reaching significant difference. Therefore, the effectiveness of KCI for breast-milk lactation could not be generally categorized as less than that of MME.
[Conclusion] MA demonstrated that KCI was more effective in decreasing post-labor pains than was MME. We could not implement the comparable study in safety at this time. Therefore, further analysis on KCI including safety may be required to argue total effectiveness on postpartum control.

Objective: If product information provided by pharmaceutical manufactures is not consistent with a product assessment made by the Pharmaceuticals and Medical Devices Agency (PMDA), users may gain false perceptions about the product, which may be detrimental to patients.  An investigation was conducted to compare the contents of product information provided by pharmaceutical manufacturers and product evaluation reports prepared by PMDA to identify any discrepancies between data assessment in the two documents.
Methods: Descriptions in “Product Characteristics” and “Clinical Studies” of product information summaries were compared with product evaluation reports prepared by PMDA.  Inquiries were addressed to manufacturers if any questions arose.
Results: The investigation was conducted on 66 new active ingredients approved in 2009 to 2010.  As 14 questions arose with 12 ingredients, inquiries were addressed to manufacturers, all of whom offered a response.  As a result, four questions were resolved for two ingredients.  However, for the remaining products, it was revealed that the manufacturers described in the product information summaries what they claimed at the time of submission even though their claims were not accepted by PMDA.
Conclusion: It was considered that the pharmaceutical manufacturers possibly did not comprehend the contents of the PMDA’s evaluation reports.  It was suggested that the industry as a whole should examine the issue.  As discrepancies were observed even in product information summaries, which are viewed by a relatively large number of people, it was assumed that more issues may be found in promotional materials provided exclusively to healthcare professionals.

Introduction: A health assessment sheet was developed to establish a new method for post marketing surveillance (PMS) for nonprescription drugs, the status of which has recently been switched from prescription (Rx) to over-the-counter (OTC) to confirm the efficacy and safety of Rx-to-OTC switched drugs.  The assessment sheet was designed to evaluate adverse reactions that may be possibly induced by the drugs and to elicit spontaneous complaints from consumers.  An investigation using the assessment sheet had been conducted earlier for famotidine tablets.  While the earlier investigation suggested the effectiveness of the assessment method, it also revealed some issues.  After making improvements in the assessment sheet, another investigation was conducted for Loxonin®S.
Method: Purchasers of Loxonin®S were asked to tick symptoms that were applicable to them among those listed in the sheet.  They were asked to revisit the pharmacy and complete the sheet for the second time after drug administration.  The possibility of adverse reactions was considered for the symptoms additionally chosen at the second visit and they were then compared with the adverse reactions described in the package insert of Loxonin®S.
Results: Total 284 people completed the health assessment sheet at their first and second visits.  Of them, 44 people (15.5%) reported additional symptoms at the second visit.  Commonly reported symptom was “frequent experience of sleepiness,” “persistent headaches” and “fatigability.”
Conclusion: The study suggested that the health assessment sheet can be an effective tool for PMS for nonprescription drugs immediately after the Rx-to-OTC switch and contributes to detecting adverse reactions of the drugs.

When establishing new pharmacy services, they must be in line with the needs of individual community residents. In our research, it was clear that services provided by the newly implemented health support pharmacies and primary care pharmacist system in recent years satisfy the needs of patients as well as the public in general. We collected information via a survey that used a structured questionnaire. In addition to basic information (age/sex), it also covered details of their pharmacy use, their thoughts on pharmacy services, and the actual usability of pharmacy services. Differences in respondent’s opinions and the actual usability of each pharmacy service were compared between age groups and sexes. Female respondents had more favorable opinions about the antismoking, nutrition, and sickness prevention consultation services than male respondents did. The proportion of survey respondents in their 40s and 50s who proactively used pension and welfare consultation services was significantly higher than for other age groups. The younger generation perceived 24-hour pharmacies and the primary care pharmacy system as necessary. There is a large disparity between people’s thoughts and opinions on the actual usability of the services that primary care pharmacies aim to offer, and this differ in people’s ages and sexes. The younger generation tend to expect the pharmacy services. It is important for pharmacies to address the needs of the generation which is skeptical toward the separation of medical and dispensary practice and recognize them the new role of pharmacies.