Objective : Post-marketing surveillance was conducted for the purpose of demonstrating the relationship between the therapeutic effect of natural IFN-β preparation on chronic active hepatitis C and HCV subtype or viral load as well as various predictors of its efficacy.
Design : Cohort studies.
Methods : Questionnaires were sent to all medical institutions at which IFN-β ('IFNβMochida') was administered to patients with chronic active hepatitis C once daily for at least 8 weeks and its therapeutic effect was judged based on the rate of virological sustained response (VSR) and the rate of biochemical (ALT) sustained response (BSR).
Results : Questionnaires for 2, 076 patients were collected from 244 medical institutions all over the country. Of these questionnaires, those for 1, 503 patients, 930 men (61.9%) and 573 women (38.1%), collected from 229 institutions could be evaluated regarding the therapeutic effect of IFNβ Mochida. The patients' mean age was 50.2 years. The average VSR were 31% for all of the patients (1, 503 patients), 61% for those with a low viral load (HCV-RNA level before IFN treatment ; <106 copies/ml) and 14% for those with a high viral load (≥106 copies/ml) ; with the subtypes 1 b, 2 a and 2 b accounting for 18, 55 and 29% respectively. BSR were 45, 69 and 32%, respectively ; with the subtypes 1 b, 2 a and 2 b accounting for 32, 66 and 56%. As for the therapeutic effect in patients with the same level of viral load but different viral subtype, at each level of viral load VSR was the highest in subtype 2 a, followed by 2 b and 1 b, showing a significant difference between 2 a and 1 b or 2 b, depending on the level of viral load. BSR of 2 a and 2 b were similarly high, showing a significant difference between 2 a or 2 b and 1 b, depending on the level of viral load. In patients with subtype 1 a or 1 b, patients who were administered IFN-β≥339 MU obtained a higher VSR than those who were administered IFN-β ≤336MU. Adverse drug reactions were observed in 89% of the total 2, 076 patients, however, these symptoms disappeared immediately after the completion of the treatment. Univariate and multivariate logistic regression analyses conducted to detect the predictors on the therapeutic effect (VSR) of IFN-β revealed that the subtype, viral load and age were significant factors for all the patients and that the viral load and NS5A mutation were significant factors for the patients with subtype 1 b. However, the NS5A mutant type viral load was significantly less than that of the other types, showing no difference in the therapeutic effect in the comparison at the same level of viral load.
Conclusion : It was confirmed that the therapeutic effect of the natural IFN-β preparation on chronic active hepatitis C varied widely depending on the viral load and viral subtype. This information will play an important role in the development of therapy for chronic hepatitis C in the future.

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The history of pharmacoepidemiology in Japan is short, and despite its importance for physicians in prescribing medicine in daily clinical work, their interest in this evidence-based science has been far from social acceptance. Pharmacoepidemiology itself especially in Japan must be firmly established with systematically constructed harmonious features defined by pharmaceutical health promotion consisting of four independent facets ; health professionals, consumer, industry and regulatory faces. Also, pharmacoepidemiology has to be developed on a scientific basis for outcome research focusing on the clinical and economic consequences of drug therapy decisions. Persuing this aim, pharmacoepidemiology will need to simultaneously invoke principles in other scientific fields such as molecular biology, biostatistics and genetic epidemiology. Ultimately, these interdisciplinary synergies can contribute to intelligent and hopefully more efficient drug development, and a better understanding of what will happen when the drug goes to market. In the clinical field of cardiology, on the other hand, numerous facets are involved in pharmacoepidemiology ; PMDS, polypharmacy and genetic aspects in gene polymorphism with special regard to LQT syndrome and anticoagulation with warfarin. These clinical factors associated with pharmacoepidemiology are summarized and discussed in detail.

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The necessity of the methodology to manage and objectively evaluate outcomes is recognized for practicing cost-effective quality care. When outcome management is applied to pharmaceutical therapy, it is important to understand the relationship between outcome management and pharmacoeconomics. Pharmacoeconomics is a tool not only to evaluate the economical efficiency of pharmaceuticals themselves but also to evaluate the efficiency of clinical pharmaceutical interventions by medical staff. To apply outcome management and pharmacoeconomics in practice, it is necessary to systemize the contents of pharmaceutical care linkied to related outcomes and to continuously document the required information for the analysis and evaluation of outcomes.

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Objective : To identify the issues in conducting pharmacoeconomics (PE) studies at pharmaceutical companies in Japan.
Methods : A questionnaire survey on the conditions of PE studies was conducted for the pharmaceutical companies that are members in the Pharmaceutical Manufacturers Association of Tokyo. Seventy-seven of 94 member companies participated, an 82% response rate. The survey covered the following topics with regard to the companies : the number of applications of PE data for the new drug pricing process, the timing and phases to conduct a PE analysis, a recognition of the necessity for PE analysis, and issues for conducting optimum PE analysis.
Results : Out of 77 responding companies, 36 companies (47%) answered that they conduct PE analysis at their regulatory affair department in order to submit supplemental applications for the drug pricing process to the Ministry of Health, Labor and Welfare. However, only 42% companies of approved drugs since April 1997 were actually submitted with PE data for the drug pricing review. Seventy-seven percent of companies recognized the necessity for PE analysis for the drugs. On the other hand, they did not perceive PE as a useful tool for negotiating drug prices with the Japanese government. Major issues for PE analysis to be conducted are ; lack of Japanese guidelines and epidemiological databases, lack of transparency in the method which reflects the data for the policy making, and lack of companies'initiative.
Conclusion : Establishment of a Japanese guideline for PE studies will be important for companies to conduct accurate and reliable PE studies. The Japanese government should disclose the process of using the PE data for policy making. At the same time, it is necessary for the companies to be more spontaneous in their PE studies.

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Although pharmacoeconomic studies are used for policy decision-making such as reimbursement and pricing decisions in several industrialized countries, they have not yet been used in an explicit way in Japan. In this article, the general methodology to interpret the results of cost-effectiveness analyses, the present situation of the usage of those analyses in the government policy of other countries, and the potential and problems of their application to policy making in Japan, are discussed.
It should be noted that other factors are considered in the decision-making process, such as clinical need, equity of access, the “rule of rescue”, and the total cost to the health care system. However, it is inappropriate to ignore the viewpoint of cost-effectiveness with regards to the budget constraint. The establishment of guidelines for the submission of pharmacoeconomic studies is necessary to ensure their validity, which leads to improved transparency of the process of health policy making.

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Objective : A major challenge to the usefulness of economic evaluation for decision-making is concern over the generalisability of the results. The purpose of this paper is to review the methodological issue of generalisability within economic evaluation and to discuss approaches for facilitating the generalisability of economic analysis to the Japanese context.
Methods : Electronic searches of key databases (MEDLINE, HEALTHSTAR, OHE, NHS EED) and handsearches of key health economics and health technology journals (ISTAHC, Pharmacoeconomics, Health Economics) in the period 1990-2000 were conducted to identify papers relating to factors affecting and methods for enhancing generalisability across three dimensions : (i) from study to practice, (ii) between location and (iii) across time. These papers were critically reviewed and the information combined into a structured commentary.
Results : Several factors can potentially limit the generalisability of results including differences in epidemiology, the availability of treatments, clinical practice patterns, relative prices and incentives to healthcare professionals and institutions. Several analytical approaches are in existence, which allow the generalisation of health economic data to any local decision-making context. These include statistical analysis of data from multinational clinical-economic trials, the use of economic modelling and the systematic review of economic data.
Conclusion : Further research in the area of generalisability will add to the credibility and usefulness of economic evaluations in general and give decision-makers confidence that the data are suitable for use as a basis for resource-allocation decisions and provide some comfort that the actions arising from their use are not misguided.

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