Cost-Effectiveness of the Adjuvant Recombinant Zoster Vaccine in Japanese Adults Aged 65 Years and Older.

INTRODUCTION: The incidence of herpes zoster (HZ) rises steeply after the age of 50 years and the number of HZ cases and complications such as postherpetic neuralgia (PHN) is predicted to increase because of the ageing population. The objective of this study was to estimate the cost-effectiveness of recombinant zoster vaccine (RZV) compared with no vaccine for the Japanese population aged ≥ 65 years. METHODS: A multi-cohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of 1 million people aged ≥ 65 years over their remaining lifetime. Vaccination at ≥ 65 years was used in alignment with the influenza and pneumococcal vaccines recommended from 65 years. Japan-specific data inputs for the model were obtained from local data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% with a second dose compliance of 95%. Costs and outcomes were discounted at 2% annually and the incremental cost-effectiveness ratio (ICER) was calculated from both a payer's and the societal perspective. Sensitivity analyses were carried out to explore the overall uncertainty in the model. RESULTS: Vaccination with RZV was projected to prevent 48,943 HZ cases and 12,136 PHN cases per million people aged ≥ 65 years compared with no vaccination. The incremental costs and quality-adjusted life years (QALYs) gained were ¥9.99 billion and 2314 QALYs from a payer's perspective and ¥9.34 billion and 2314 QALYs from a societal perspective. The resulting ICERs were approximately ¥4,320,000 and ¥4,040,000 per QALY gained from a payer's and the societal perspective, respectively. The ICER remained below a willingness-to-pay threshold of ¥5,000,000 for most sensitivity analyses carried out. CONCLUSION: Vaccination against HZ with RZV would be cost-effective compared with no vaccination for the Japanese population aged ≥ 65 years. TRIAL REGISTRATION: GSK study identifier: HO-16-17837. FUNDING: GlaxoSmithKline Biologicals SA.

[Problems with Advertisements for Health Foods].

We have been studying the way advertisements for medicines have been monitored by the Health, Labour and Welfare Sciences Research Grants. In the last fiscal year, we identified products that were being advertised to general consumers, such as OTC drugs and designated quasi-drugs, and made recommendations to the Ministry of Health, Labour and Welfare on the methods of advertisement. Members of our research group, including physicians, pharmacists, and consumers, pointed out that advertisements for so-called health foods and foods with functional claims were much more unregulated than those for drugs, including OTC drugs. Thus, this fiscal year, we decided to focus on health foods. Advertisements for health foods are regulated by the Health Promotion Act and the Act against Unjustifiable Premiums and Misleading Representations; moreover, in many cases, cautions are issued by the Consumer Affairs Agency or prefectures. Several studies also reported health damage in patients who, because of their belief in advertisements, intentionally discontinued treatment or missed the opportunity to receive appropriate medical treatment. Here, we report inappropriate advertisements for health foods that may cause health hazards.

The Potential Public Health Impact of Herpes Zoster Vaccination of People Aged ≥ 50 Years in Japan: Results of a Markov Model Analysis.

INTRODUCTION: The aim of this study was to compare the public health impact of introducing two herpes zoster (HZ) vaccines into the vaccination programs for the Japanese population aged ≥ 50 years: a single-dose Varicella Vaccine Live (VVL) or a two-dose adjuvanted Recombinant Zoster Vaccine (RZV). METHODS: A multi-cohort static Markov model was developed to follow age cohorts (50-59, 60-69, 70-79 and ≥ 80 years) over their remaining lifetime. Japan-specific data inputs for the model were obtained from Japanese data sources. Age-stratified vaccine efficacy and waning rates were based on published clinical trial data. In the base-case analysis, vaccine coverage was assumed to be 40% for both vaccines, and compliance with second-dose of the RZV vaccine was set to 95%. RESULTS: Vaccination with RZV was projected to prevent approximately 3.3 million HZ cases, 692,000 cases of postherpetic neuralgia (PHN), and 281,000 cases of other complications, compared with the prevention of 0.8 million HZ cases, 216,000 PHN cases, and 57,000 other complications with vaccination with VVL. The number of individuals needed to vaccinate in order to prevent one HZ case ranged from 6 to 14 using RZV (depending on age and assumed second-dose compliance) and from 21 to 138 depending on age using VVL. By preventing a higher number of HZ cases and its complications, RZV vaccination led to fewer outpatient visits and hospitalizations than vaccination with VVL. CONCLUSION: Both vaccines had a positive public health impact compared to no vaccination, but due to its higher vaccine efficacy, RZV demonstrated a superior public health impact compared with VVL. FUNDING: GlaxoSmithKline Biologicals SA.

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.

Cost-Effectiveness Evaluation of the 10-Valent Pneumococcal Non-typeable Haemophilus influenzae Protein D Conjugate Vaccine and 13-Valent Pneumococcal Vaccine in Japanese Children.

INTRODUCTION: Diseases caused by Streptococcus pneumoniae represent a major public health problem. The purpose of this study was to compare, in the Japanese context, the projected health benefits, costs and cost-effectiveness of the latest generation of pneumococcal conjugate vaccines which may provide important insight into the potential public health impact of interventions in the context of local disease-specific epidemiology. METHODS: A Markov model was used to compare two vaccination strategies which involve routine infant immunization with either the 13-valent pneumococcal conjugate vaccine (PCV-13; Prevenar 13™, Pfizer, Pearl River, NY, USA) or the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Biologicals SA, Rixensart, Belgium) over a time horizon of 5 years from the healthcare provider and societal perspectives. Estimates for key model parameters were obtained from locally available databases and published literature. Incremental benefits in terms of costs and quality-adjusted life-year and cost-effectiveness were assessed. RESULTS: A 3 + 1 vaccination schedule for infants with PHiD-CV is expected to have a similar impact on invasive pneumococcal disease and pneumonia and a larger impact on acute otitis media-related outcomes compared with PCV-13. Assuming price parity for these vaccines, the model projected that vaccination with PHiD-CV would result in cost savings of 1.9 and 3.9 billion Japanese yen from the provider and societal perspectives, respectively. This was largely due to a reduction in highly prevalent acute otitis media. Vaccination with PHiD-CV was expected to generate a gain of 433 quality-adjusted life-years compared to PCV-13 translating into dominance over PCV-13. Sensitivity analyses showed robustness of model outcome to changes in key model parameters and substantiated that the model outcome was consistently driven by the incremental benefit of PHiD-CV in averting acute otitis media. CONCLUSION: In comparison to PCV-13, vaccination with PHiD-CV is projected to be cost saving for Japan from both the healthcare provider and societal perspectives.

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.

OBJECTIVES: Do 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. METHODS: The 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. RESULTS: In 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). CONCLUSIONS: The study suggested the possibility that ASPs contributed to the reduction of the antimicrobial therapy costs in a community hospital with 429 beds.

Acceptable incremental cost effectiveness ratio for use of new drugs, cases in statin therapies.

As it is an urgent issue to contain increasing healthcare expenditures, unlimited reimbursement of pharmaceuticals continues to be controversial. The objective of this study is to identify acceptable incremental cost effectiveness ratios between new and conventional therapies. Clinical study data for five statin therapies were used to indicate treatment effectiveness and incremental costs were indicated by price premiums at price listing. The incremental cost effectiveness ratios to pravastatin were 0 yen/patient with response, 1,475.1 yen/patient with response, 3,033.3 yen/patient with response, and 3,032.4 yen/patient with response. By conducting further analyses in various pharmaceuticals and categorizing acceptable incremental cost effectiveness ratios based on the disease severity and expected level of improvement in disease condition, drug prices that reflect the value of new pharmaceuticals and that are reasonable to be reimbursed can be suggested.

[Detection of adverse drug reactions with the use of a simple questionnaire].

In order to detect adverse events in patients at pharmacies, a questionnaire was developed to evaluate adverse drug reactions that may come from the use of pharmaceuticals. The questionnaire enabled pharmacists to assume possible adverse drug reactions while they dispense a prescription but was designed not to make patients sensitive. An investigation method was developed to detect adverse drug reactions that may be attributable to drug treatment by leading patient natural complaints while pharmacists provide drug treatment guidance to patients. This investigation was conducted at six pharmacies. As a result, 26.6% of the adverse drug reactions that can be associated with the question items ticked by at least five patients who had received the same drug were not indicated in the precautionary statements of the drugs. This suggests that this investigation may possibly contribute to detection of unknown adverse drug reactions. Furthermore, some of the patients who ticked question items related to prodromal symptoms of serious adverse drug reactions had received drug therapies that were known to be associated with those adverse drug reactions. This also suggests that the investigation may possibly contribute to detection of serious adverse drug reactions. It was considered to be more effective to focus on detection of serious adverse drug reactions with the use of the questionnaire in the future, which is more important than safety precautions. The accuracy in judging adverse drug reactions can be enhanced by asking patients with chronic diseases to respond to the questionnaire every time a prescription is dispensed.

[Cost-effectiveness of salmeterol/fluticasone combination therapy vs. fluticasone propionate in Japanese asthmatic patients].

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.

[Patient needs for consultation with pharmacists].

More prescription drugs are dispensed by pharmacists rather than doctors in response to government healthcare reform. However, the results of our preliminary survey suggested a hypothesis that patients were not always satisfied with explanations provided by pharmacists upon dispensing, and therefore patient satisfaction might be enhanced if pharmacists spent more time on consultation services. The survey was conducted in 1,800 people. 321 people (17.8%) answered that pharmacist explanations were not sufficient or that they expected further consultation with pharmacists. The most common reason why they did not ask for consultation was that other patients were waiting (41.7%). If up to 30-minute consultation service was available at a pharmacy where patient privacy was ensured, 898 people (49.9%) answered that they wanted to use the service. The average willingness-to-pay (WTP) for the service was 338 yen and the mean WTP was 400 yen. When those who answered 0 yen were excluded, the average was 386 yen and the mean was 400 yen. The online survey revealed that some patients were not satisfied with pharmacist explanations upon dispensing, and that there was a need for consultation services at pharmacies. Many of the reasons why patients did not ask for consultation although they wanted to were attributable to pharmacies, and the survey results suggested a need for improvement in their services. In view of the WTP for the service, it is considered worthwhile to discuss the introduction of such a system for consultation services into dispensing fee.

[Reasonable dispensing fee for patients].

The actual pharmacist workload is not always reflected in dispensing fees, while patients do not always understand the system of dispensing fees. In this study, the relation between the time required for dispensing and prescription details and that between the time required for instruction on drug administration and instruction details in nine pharmacies in Chiba prefecture were investigated. As a result of linear regression analysis, it was suggested that, compared with doses, the number of drug items more greatly affected the time required for dispensing. For oral drugs, the following relation was suggested in the study: [dispensing time (sec)]=29.3+27.5 x [number of items]+0.7 x[dosing days]+94.4 x [number of items]+7.1 x [dosing days]. Based on the actual dispensing fees claimed, fees per second of dispensing were estimated at 0.7 point. For drug administration instruction, it was considered reasonable to classify instructions into three categories according to the instruction details and set fees by the categories. When any further pharmaceutical expertise is required, fees should not be set according to the workload but additional fees should be provided to reward expertise.

Pharmacoeconomic analysis of hypertriglyceridemia treatment at medical institutions.

It has been demonstrated that HMG-CoA reductase inhibitors effectively decrease low density lipoprotein and total cholesterol levels, and presently, HMG-CoA reductase inhibitors are most widely used in hyperlipidemia treatment. On the other hand, it has been demonstrated that fibrate agents decrease triglyceride levels more effectively compared to HMG-CoA reductase inhibitors. A cost-effectiveness study comparing fenofibrate, a fibrate agent, and atorvastatin was therefore conducted in hypertriglyceridemia patients. Referring to an analytical method published in the UK, the percentage of patients received fenofibrate and atorvastatin treatments at each dose level was estimated from prescription records at the medical institutions investigated. Changes in the total cholesterol and triglyceride values after the drug administration were investigated examining published reports. Based on the said data, the treatment effectiveness was measured by the percentage of patients who achieved the target lipid levels. The treatment costs were estimated based on the number of patients investigated and reimbursement prices of the drugs. The incremental cost-effectiveness ratio of fenofibrate in decreasing triglyceride levels was dominant over atorvastatin. The incremental cost-effectiveness ratio of atorvastatin in decreasing low density lipoprotein cholesterol levels was JPY 69911. This provides a model for choosing drug treatments that reflects clinical practices at medical institutions by substituting figures for individual cases.

Contributions of pharmacists through the promotion of proper drug use.

The contents of pharmacist interventions, which were carried out by the ward pharmacists in their routine pharmacy service activities, were sorted and analyzed to evaluate the contributions of pharmacists. In the ward where pharmacists were stationed, there were a total of 196 cases of pharmacist intervention. The prescription was changed in 170 cases, giving a rate of prescription change of 86.7%. The breakdown of the pharmacist intervention was as follows: "efficacy/safety", 106 cases, followed by "dosage regimen" (48 cases) and "compliance" (10 cases). Cost savings achieved during the investigation period were calculated to be 440,639 yen, and cost avoidance was valued at 1,941,847-3,883,695 yen using the Diagnosis Procedure Combination (DPC). The results of the present investigation showed that pharmacists contribute to through not only their pharmacy services, but also through the promotion of proper drug use and risk management, thereby contributing to hospital management through cost savings and avoidance.

Objective evaluation of generic-specific drug information.

Growth in the use of generic drugs remains flat in Japan, and one of the reasons cited is information availability. We previously showed that the amount of information available on generic drugs differs greatly from one pharmaceutical industry to another, though, on average, it is inferior to that for original, brand name drugs. This report looks at information on individual generic drug products, rather than the active ingredients contained therein. In May 2004, we studied ingredients sold by at least 20 pharmaceutical industries. Here, for the same, particular ingredient, we evaluate current availability of generic-specific information (as of August 2005), as well as change over time. On the basis of ingredient, the amount of information provided for generic drugs is 31.1+/-17.5-57.3+/-11.7% that for the corresponding original drugs (Mean+/-S.D.), but in the company-by-company comparison, a large dispersion of 16.6+/-5.0-69.4+/-11.9% (Mean +/-S.D.) is observed. In terms of information content, generic drugs provided less than 50% as much information on "drug interactions", "clinical efficacy", and "outline of side effects", as that for original drugs. The difference between generic and original drugs was smaller in comparisons focusing on information specific to generics than on those including all drug information. Our study also revealed that, over time, some pharmaceutical industries have added to the amount of information provided. When information is a deciding factor, the quantity available at the current time is not the only relevant aspect; it is best to select a pharmaceutical industry that is proactive about supplementing information post-release.

[Cost-effectiveness of fluticasone propionate for asthma episodes in Japanese patients with asthma--Fluticasone Investigation of Asthma Episode (FINE) study].

BACKGROUND: To discuss and estimate the economic benefits gained by fluticasone propionate (FP) for patients with asthma over hospitalization, emergency room visit, unscheduled visit, and absence (representative by asthma-related episode). METHOD: Asthma-related episodes in pre and post 6 months of FP use were derived from a survey of FP on asthma-related episodes (FINE study). Medical cost was evaluated by macro-cost estimate and productivity loss by human capital approach. RESULTS: Discussion of asthma-related episodes in-between before and after the use of FP in eight hundred ninety-eight valuable subjects revealed that FP use significantly reduced asthma-related episodic costs of approximately 120,000 yen (p<0.001), whereas total drug acquisition costs for being newly consumed FP, leukotriene receptor antagonists, inhaled short-acting beta2 agonists, etc were significantly increased by approximately 16,000 yen. Moreover, while significantly avoiding productivity loss of approximately about 35,000 yen it totally provided cost-savings of about 70,000 yen at the patients' viewpoint. When sensitivity analyses were performed by adjusting the confounding factors using analysis of covariance, the aforementioned base case results might be persistent. For safety of FP, some adverse events related to the use of FP were identified of about 2.0%, and there were not any serious ones at all. CONCLUSION: The economic evaluation of FP demonstrated that it is sufficient, whereas an acquisition cost was increased. Use of FP economically impacts on Japanese society and patients.

The realities and medical expense of hospitalization that originates in outpatient medicine treatment.

Problems associated with outpatient pharmacotherapy may require hospitalization. However, such hospitalization may be prevented if pharmacist's pharmaceutical care (PC) is given. We investigated the reasons for hospitalization in medical institutions and medical expenses were calculated. Inpatient diagnoses, treatment, etc. in the previous year in the past were examined, and cases of hospitalization due to drug therapy were extracted. Next, the possibility of preventing hospitalization with PC practice was examined. Among 1552 cases, outpatient pharmacotherapy was the reason for hospitalization in 27 cases. Noncompliance was the underlying cause in about 40% of hospitalizations. It was thought that in 22 cases hospitalization could have been prevented by pharmacist's PC. The average hospitalization medical expense was 295,805 yen per patient. It is necessary to perform regular consultation recommendations, interventions with the family, home care, etc. for proactive PC.

Cost-effectiveness of including salmeterol in asthma therapy in a primary care setting in Japan.

To discuss and estimate the clinical and economic benefits obtained during combination therapy with inhaled corticosteroids (ICS) plus salmeterol (SLM) for Japanese patients with asthma on the basis of the Global Initiative for Asthma (GINA) Guidelines. Fifty-four cases aged>16 years with either moderate persistent asthma (step 3) or severe persistent asthma (step 4) were assessed in a retrospective survey. Participants must have been a patient at the author's clinic continuously from June 2001 and been users of SLM for more than one year. Signed informed consent was obtained. Both clinical and economic components of SLM use in asthma therapy over the past two years were evaluated. Cost analyses revealed that SLM use significantly reduced medical costs of leukotriene receptor antagonist and short-acting inhaled beta(2)-agonists. Moreover, clinical outcomes (e.g. symptom-free day) were significantly improved after initiation of SLM. Sensitivity analyses confirmed that use of SLM is cost-effective. Combination therapy with inhaled corticosteroids and SLM on the basis of GINA guidelines appears to be efficacious and cost effective for the treatment of moderate or severe persistent asthma in Japanese patients.

[Evaluation of information for generic drugs based on importance and necessity].

Limited use of generics in Japan has been justified on the basis of problematic quality, distribution and information. Of these three problem areas, the state of provision of information in particular has never been objectively evaluated. We therefore sought to evaluate information according to its necessity and importance to medical practice. To establish criteria for evaluation, we weighted 36 separate pieces of drug information found in package inserts and interview forms according to necessity and importance, based on the results of a survey of nationwide medical institutions with DI offices. We then used the evaluation criteria to evaluate currently available drugs with 20 or more products per formulation. We evaluated 14 formulations (324 products). Generic drugs were found to have 25.3+/-18.7 to 46.1+/-14.2% (Mean+/-S.D.) the information of brand name drugs when products were compared for quantity of information by formulation. However, comparison according to manufacturer returned a larger range of variation at 14.4+/-8.6 to 64.3+/-14.2% (Mean+/-S.D.). These data reveal that manufacturer differences play a large role in the provision of drug information. Drug information was also compared separately by category for both brand name and generic drugs. Generic drugs were found to have insufficient information on clinical data, pharmacokinetics, safety, side effects, and nonclinical tests. Brand name drugs also scored low points for information on pharmacokinetics. It is imperative that both brand name and generic drugs provide more information on pharmacokinetics.