Published papers

Background: Gabapentinoids (GBP) and benzodiazepines (BZ) are commonly prescribed in older adults and their package inserts list edema and vertigo as adverse drug reactions. These adverse drug reactions may be treated with symptomatic drug therapies without discontinuing the culprit drugs or decreasing their dose, thereby initiating a prescribing cascade and often resulting in polypharmacy. Whether prescribing cascades occur in the treatment of edema and dizziness among Japanese patients treated with GBP and BZ has not been investigated, including treatment with mirogabalin, a class drug of GBP marketed in Japan. Objective: We aimed to investigate prescribing cascades with GBP-induced and BZ-induced edema and dizziness treated with loop diuretics (LD) and anti-vertigo drugs (AVD), respectively, among older adults. Methods: A prescription sequence symmetry analysis design was used to detect signals of prescribing cascades associated with edema and dizziness induced by GBP and BZ (exposure drugs). Loop diuretics and AVD were the outcome drugs used to identify prescribing cascades following the initiation of exposure drugs. The study population consisted of enrollees of a large-scale health claims database provided by DeSC Healthcare, Inc., between April 2014 and March 2021. Subjects eligible for a prescription sequence symmetry analysis were patients aged ≥ 65 years prescribed an outcome drug within 90 days before and after exposure drug initiation. A signal of a prescribing cascade was detected if secular trend-adjusted sequence ratios were statistically significant on comparison of the frequencies of outcome drug initiation before and after exposure drug initiation. Results: We identified 2671 patients with prescriptions of a GBP-LD combination, 4009 with a GBP-AVD combination, 8675 with a BZ-LD combination, and 9462 with a BZ-AVD combination. The adjusted sequence ratios for GBP-LD and BZ-LD cascades were significantly larger than one (adjusted sequence ratio [95% confidence interval], 1.69 [1.56–1.83]; 1.35 [1.29–1.41], respectively), indicating positive signals of prescribing cascades. No signal was detected for the GBP-AVD or BZ-AVD cascade (0.89 [0.83–0.94]; 0.90 [0.87–0.94], respectively). The adjusted sequence ratio for the mirogabalin cascade was higher than that for pregabalin (2.23 [1.84–2.71] vs 1.59 [1.46–1.73]). Conclusions: Our study provides good evidence that LD-prescribing cascades associated with edema would be a class effect of GBP and BZ. Edema emerging around 1 month after GBP initiation should be carefully differentiated from pathological edema, and undue LD prescription as a prescribing cascade should be avoided.

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. In this paper, we aim to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy, gold/reference standards, study size, prioritization of accuracy measures, algorithm portability, and implications for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome, or covariate). Validation work should be part of routine maintenance of RWD sources. This article is part of a Special Collection on Pharmacoepidemiology.

AbstractObjectives The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. Materials and methods Our analysis compared the ‘EGFR testing strategy’, in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the ‘no-testing strategy,’ in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. Results The incremental cost and effectiveness per patient of the ‘EGFR testing strategy’ compared to the ‘no-testing strategy’ was estimated to be approximately JP¥122,000 (US$1180; US$1 = JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the ‘EGFR testing strategy’ is cost-effective compared with the ‘no-testing strategy’ when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. Conclusion The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin–paclitaxel for the treatment for NSCLC in Japan.

Currently, self-medication, including the use of foods with health claims (FHCs), is promoted as means of increasing our health span. However, the functional substance(s) in FHCs and its actions are diverse, and therefore it is difficult to evaluate their safety and efficacy in clinical trials. In this review article, we describe the definition and the history of regulations regarding FHCs. After discussing their types and features, we explain the differences on regulations between FHCs and ethical pharmaceuticals regarding their safety and efficacy in clinical trials, which are required to provide them with scientific evidence. Finally, we believe that transparent standards regarding the evaluation of FHCs would help increase the use of FHCs and their market value in the future.

薬剤疫学は、各国における薬事制度に立脚し、おもに日常診療で得られるデータReal World Data(RWD)に基づき、医薬品の市販後安全性確保と適正使用に資するエビデンスの創生を目的とする学問である。しかし、この分野では新医薬品の承認審査への応用をめざすエビデンス創出についてはほとんど議論されてこなかった。2017年2月にICHが公表したGCP renovationでは、RWDを用いた観察研究を含むさまざまな研究デザインにより生み出されるエビデンスを薬事承認申請に用いる方針が示され、これらのあらたな研究デザインに関する規定が次世代のGCPに盛り込まれることが謳われている。本稿では、薬事上の意思決定において、利用目的に応じたデータ品質水準、Fit-for-purpose data qualityの観点から、RWDを利用する際に求められるデータ品質に関する考察を行う。(著者抄録)

Background: According to the Codex Alimentarius of the foods with health claims (FHCs), two major factors play a significant role in the ability for consumers to select functional foods and utilize them appropriately for health maintenance (Codex Alimentarius, 1997). These are: 1) food labeling based on scientific evidence that consumers are able to understand; and 2) standardized criteria for obtaining scientific evidence. Scope and approach: We discuss the regulatory system for foods with health claims in the world and the need for consumer science and regulatory science research through reviewing the history and recent topics about the regulation on FHCs in Japan. Key findings and conclusions: There are some differences in regulations on FHCs among countries participating in the Codex, which have been said sometimes to cause some troubles. These are: 1) despite of the lack of renewal system, Japan experienced the first revocation event regarding the approved Foods for Specified Health Uses category of FHCs in 2016; and 2) global export barriers. Therefore, the introduction of mutual recognition rules among countries has been desired in Japan for further international harmonization. However, its feasibility seems to be low because of the complexity caused by such differences on regulations among countries. When it happens, we expect that the global regulatory climates on FHCs may be better regulated by involving neutral academic researchers and the trained experts in the field of consumer and regulatory science of functional foods. As Japan is the first country to establish the FHCs regulatory system in the world, it should lead to discuss the introduction of mutual recognition rules with other countries immediately. (C) 2017 Elsevier Ltd. All rights reserved.

© 2019 Toshiki Fukasawa et al. T. Background: The Japanese Ministry of Health, Labour and Welfare introduced Specific Health Checkups (SHC) to identify individuals at risk of metabolic syndrome (MS). This study aimed to describe the SHC database developed by the Japan Medical Data Center Co., Ltd. (JMDC) as a means of exploring lifestyle behaviors and lifestyle diseases among working generations. Methods: We conducted a retrospective, cross-sectional study of employees and their families using the JMDC-SHC database to describe the prevalence of lifestyle behaviors (smoking, exercise, dietary habits, drinking habits, and sleeping) and lifestyle diseases (MS, hypertension, dyslipidemia, and diabetes mellitus). Results were compared with data from the 2015 National Health and Nutrition Survey (NHNS) in Japan as a benchmark. Results: All 646,869 enrollees in the JMDC-SHC database were included, of whom 66.5% were men. Age ranged from 40–74 years. Compared with the results of the NHNS, the JMDC-SHC subjects were younger and had fewer MS components and a lower prevalence of diabetes and hypertension. Subjects in their 40s were most likely to have unhealthy lifestyle behaviors in all age groups (eg, smoking: 41.0% in men and 10.2% in women). The SHC group had more favorable behaviors overall, but underweight was more prevalent in the SHC females. Conclusions: The JMDC-SHC population showed different lifestyle and lifestyle disease profiles to the NHNS population, probably due to its different age, gender, and employment distributions. Development of healthcare policies and plans for working generations would benefit from the selection of an age-and employment-appropriate database.