Sachiko Masuda

Impact of biomarker usage on oncology drug development.

What is known and Objective:  The increasing cost of drug research and development and the decreasing number of new drugs being launched are serious issues for pharmaceutical companies. Biomarkers for predicting drug effectiveness are regarded as useful tools for combating these trends. However, the extent to which these biomarkers actually help in improving drug development is unclear. Here, we investigated the efficiency of biomarker usage in oncology drug development by focusing on stratification markers.

Risk factors for sudden cardiac death among Japanese: The Circulatory Risk in Communities Study

Objective: There is little evidence concerning risk factors for sudden cardiac death (SCD) among Asians. Patients and methods: A prospective, nested, case–control study of Japanese patients aged between 30 and 84 years was undertaken using data collected from 26 870 participants in cardiovascular risk surveys conducted in four communities between 1975 and 2005. The incidence of SCD was ascertained by systematic surveillance, with 239 cases of SCD identified over this period. For each case of SCD, three control patients were selected, matched by age, sex, examination year, follow-up time, and community. Results: Hypertension, diabetes mellitus, smoking, major ST-T abnormalities, left high amplitude R waves, and increased heart rate (≥77 beat/min) were all independently associated with a 1.5–3.2-fold increase in SCD risk, whereas no associations were observed for body mass index and hypercholesterolemia. The population-attributable fraction [95% confidence interval (CI)] was 23.0% (2.9–39.0) for hypertension, 15.3% (3.8–25.5) for current smoking, 14.5% (8.0–20.5) for major ST-T abnormalities, and 8.1% (2.2–13.7) for diabetes mellitus. The number of SCD risk factors (hypertension, diabetes, smoking, and ECG abnormalities) was positively associated with increased SCD risk. The odds ratio for increased SCD risk with three or more risk factors versus zero risk factors was 5.76 (95% CI 3.20–10.39). Conclusions: Among the Japanese population, hypertension, smoking, major ST-T abnormalities, left high amplitude R waves, and diabetes mellitus were associated with an increased incidence of SCD, whereas there were no associations of body mass index or hypercholesterolemia with SCD incidence.

Anticancer drug development from traditional cytotoxic to targeted therapies: evidence of shorter drug research and development time, and shorter drug lag in Japan

What is known and Objective:  Concern about the drug lag, the delay in marketing approval between one country and another, for anticancer drugs has increased in Japan. Although a number of studies have investigated the drug lag, none has investigated it in relation to the transition of anticancer therapy from traditional cytotoxic drugs to molecularly targeted agents. Our aim was to investigate current trend in oncology drug lag between the US and Japan and identify oncology drugs approved in only one of the two countries.

Research and development productivity map: visualization of industry status

Decline in research and development (R&D) productivity and changes in the business environment have led to pharmaceutical company management to strive to improve R&D productivity. This decline is widely considered to be a major cause of industry consolidation and has received increased scholarly attention. This study aims to construct an R&D productivity map to visualize the industrys R&D productivity and to identify similarity in corporate actions with a view to investigate whether there is a relationship between deterioration in R&D productivity and industry consolidation.

Trends in cancer prognosis in a population-based cohort survey: Can recent advances in cancer therapy affect the prognosis?

BACKGROUND The aim of the study was to investigate trends in cancer prognosis by examining the relationship between period of diagnosis and probability of death from cancer in a population-based cohort. METHODS Within a cohort of Japanese men and women aged 40-69 years and free of prior diagnosis of cancer and cardiovascular disease at baseline, data from 4403 patients diagnosed with cancer between 1990 and 2006 and followed up until 2012 were analyzed using survival regression models to assess the presence of an effect of the period of diagnosis (before 1998 versus after 1998) on the risk of dying from cancer. RESULTS We noted a significant decrease in risk of dying from cancer among individuals diagnosed after 1998 with lung cancer (hazard ratio [HR]=0.676 [0.571-0.800]) or colorectal cancer (HR=0.801 [0.661-0.970]). A decrease in the estimated five-year probability of death from cancer was also noted between the first (before 1998) and the second (after 1998) period of diagnosis for lung and colorectal cancers (e.g., 85.4% vs. 73.3% for lung cancer and 44.6% vs. 37.7% for colorectal cancer, respectively, for stage III in men aged 60 at diagnosis). CONCLUSIONS This study presented the first scientific evidence of improvement in prognosis for lung and colorectal cancer patients in a population-based cohort in Japan. Our results suggest that recent advances in cancer treatment could have influenced cancer survival differently among lung, colorectal and gastric cancers.

Analyzing the generic penetration trend in the Japanese dispensing market by therapeutic category

Japanese government has started to implement several actions to promote the use of generics; however, the generic penetration rate in value advanced rather slowly from 15.4% in March 2006 to 18.7% in December 2009. Japanese pharmaceutical market has at least two unique facts which differentiate from other markets: timing of generics launch and pricing. These unique features may require a new entrant to consider the different marketing strategy. In this article, we observed that the penetration rate varies among therapeutic categories and the penetration curve for vasodilators, miscellaneous antineoplastics, and synthetic antibacterials is similar. Particularly, these categories had a launch of major original drugs within the examined period and the logistic regression for each category indicated that the reflection point of the curve was 21, 33, and 39 days after the generics launch, accordingly. As previous research suggests that the estimated sales revenue of the original drug is considered as a key determinant for generic drug penetration even in Japan. Japanese generics market will likely grow with a support of government generic promotion policy and the upcoming patent expiry of blockbusters. It is important to consider the entry strategy by therapeutic category and plan the early market penetration strategy.

The Market Exclusivity Period for New Drugs in Japan: Overview of Intellectual Property Protection and Related Regulations

This paper reviews the institutional factors in Japan that affect the market exclusivity period for new drugs. The factors which directly affect the period are (1) statutory subject matter of patent protection, (2) patent term extension, and (3) restriction of the entry of generic drugs (market exclusivity right or data protection system). Other factors include (4) the experimental use exception (the so-called Bolar provision) and (5) compulsory license. In addition, the impacts of these factors on both brand-named manufacturers and generic drug manufacturers under the specific circumstances of the Japanese pharmaceutical market, such as the influence of the healthcare insurance system or the drug price control system, are discussed.