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Background: The utilization of biomarkers has become increasingly active to enhance efficiency of clinical development. This study evaluated the current situation and quantitative impact of co-development of companion diagnostics (CDx) on the oncology drug development in Japan., Methods: Based on publicly available information about the oncology drugs and CDx approved in Japan in 2010-2020, we evaluated the approval lag time between drugs and CDx, and the duration between the pivotal study start date and the new drug application submission date (the time to application). Influences of multiple factors including the use of CDx on the time to application were also analyzed., Results: A diagnostic test was mostly used from an early development phase such as phase1/2 study, and the median approval lag has tended to decrease when approved CDx were used (- 507 vs. - 25 days for newly developed CDx). The shorter median times to application were observed in Drugs with CDx (1204 days) compared to Targeted therapies without CDx (1423 days) or Other drugs without CDx (1853 days), although both the cancer types and the implementation of multi-regional clinical trials have a larger impact on the time to application compared to the use of CDx., Conclusions: The use of CDx from the early development phase and the global development strategy could have a positive contribution on the development period of oncology drugs, which will facilitate patients' earlier access to the optimal treatment., (© 2021. The Drug Information Association, Inc.)

Purpose: The present paper describes two new genera and species of the parasitic copepod family Chondracanthidae Milne Edwards, 1840 based on specimens collected from two species of deep-sea fishes at a depth of 212 m off Suruga Bay, Japan. Avatar nishidai gen. et sp. nov. is described from the host fish Chaunax abei Le Danois, 1978 (Chaunacidae). Kokeshioides surugaensis gen. et sp. nov. is described from the host fish Setarches longimanus (Alcock, 1894) (Setarchidae)., Methods: Fresh specimens of chondracanthids were collected from the buccal cavity of two species of deep-sea fishes (fish hosts were frozen), Chaunax abei Le Danois, 1978 (Lophiiformes: Chaunacidae) and Setarches longimanus (Alcock, 1894) (Perciformes: Setarchidae), caught at a depth of 212 m in Suruga Bay, Japan (34° 37'48.87″ N, 138° 43'2.958″ E). Both the species are described and illustrated based on ovigerous females., Results: The genus Avatar gen. nov. can readily be distinguished from all other chondracanthid genera by the following combination of features: cephalothorax slightly wider than long with anterior pair of large and posterior pair of small lateral lobes, and two pairs of ventro-lateral processes; the very posteriormost part of the first pedigerous somite contributes to the neck; cylindrical trunk with two pairs of blunt proximal fusiform processes; antennule with small knob terminally; antenna bearing distal endopodal segment; labrum protruding ventrally; two pairs of biramous legs each with 2-segmented rami. Kokeshioides gen. nov. has the following combinations of features that distinguish it from other chondracanthid genera: body flattened, without lateral processes; cephalothorax much wider than long, with paired anterolateral and posterolateral lobes, folded ventrally; the very posteriormost part of the first pedigerous somite contributes to the neck; mandible elongate; legs unique, heavily sclerotized, represented by two pairs of acutely pointed processes., Conclusion: With the addition of two new genera presently reported, the family Chondracanthidae currently includes 52 valid genera. Among the described genera Avatar gen. nov. seems to be very primitive, while Kokeshioides gen. nov. is highly advanced. The deduced evolutionary history of chondracanthid genera is also discussed., (© 2024. The Author(s).)

Background: Aspiration pneumonia in older adults is increasingly common, with a high care burden and morbidity. However, clinical competencies in its management have not been developed, and healthcare professionals struggle on how to care for these patients with multimodal treatment needs. Therefore, we conducted a scoping review to investigate what is known about the desired clinical competencies for the management of older adults with aspiration pneumonia, to utilise in clinical practice, education, and future research., Methods: First, we defined aspiration pneumonia according to a preliminary search. We then searched the literature on MEDLINE and CINAHL, focusing on studies involving patients aged 65 years old and older diagnosed with aspiration pneumonia. All settings were included, with the exception of intensive care units. Publication dates were limited to January 2011 to July 2022 and languages to English and Japanese. The extracted data were used to refine the preliminary competency framework developed by the Japan Aspiration pneumonia inter-Professional team Educational Program (JAPEP) in preparation of this study., Results: Ninety-nine studies were included. Following data extraction from these studies, 3 competencies were renamed, and 3 new competencies were added, to create a list of 12 competencies. These were Diagnosis, Treatment, Swallow Assessment, Underlying condition management, Nutrition, Oral management, Rehabilitation, Multidisciplinary team, Decision making, Prevention, Prognosis, and Palliative care., Conclusions: Our scoping review identified 12 clinical competencies required in the management of older adults with aspiration pneumonia, outlined in the phrase 'Diagnose, Treat and SUPPORT'. We encourage healthcare professionals to share these competencies as a team to identify areas of unmet need and improve their patient care, with an emphasis on supportive care., (© 2023. The Author(s).)

The Ministry of Health, Labour and Welfare (MHLW) in Japan approved the first generic version of Nasonex in February 2018. The Pharmaceuticals and Medical Devices Agency requires in vitro, pharmacokinetic, and pharmacodynamic or clinical endpoint data to approve generic nasal spray drug products. However, the MHLW has not published basic principle for approving nasal generic drug products. Therefore, this article summarizes the data used for the approval of the first generic Nasonex based on publicly available data. Additionally, we compare the bioequivalence evaluations regarding the human studies based on the generic version of Nasonex between Japan and the USA., (© 2022. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Background: Digital therapeutics (DTx), the provision of treatment through mobile devices such as smartphones, have attracted great interest as a new medical modality. However, the number of authorized therapeutic applications in the US and Japan is low. Understanding the obstacles in obtaining regulatory authorizations will be the key in promoting timely development of therapeutic applications. Thus, we conducted a comprehensive analysis of the clinical study designs of therapeutic applications authorized in the US and Japan., Methods: Data on authorized therapeutic applications and the regulations involved were collated from the databases of the Food and Drug Administration (USA), Ministry of Health, Labour and Welfare (Japan), and Pharmaceuticals and Medical Devices Agency (Japan)., Results: Most therapeutic applications authorized targeted neuropsychiatric disorders and used cognitive behavioral therapy (CBT)-based treatments. All the involved clinical trials were randomized-controlled studies. Various types of controls-such as standard care, sham application, digital control, and therapies delivered by healthcare providers-were used. Both subjective and objective indices were acceptable as the primary endpoints. Long-term efficacy was evaluated, and all adverse events were assessed comprehensively. The setting up of controls and the need to study long-term efficacy depend heavily on the applications functionality and the target disease characteristics., Conclusions: This study reveals the points to be considered in planning clinical studies and regulatory strategies for authorizing therapeutic applications. Therapeutic applications can provide new therapy and have potential to solve unmet clinical needs. Our findings shed a light on efficient development and rapid commercialization of therapeutic applications., (© 2022. The Author(s).)

Purpose: The purpose of this study was to use the food intake level scale (FILS) to clarify whether calf circumference (CC) and stroke contribute to an improvement of inpatient dysphagia., Methods: We used the Japanese sarcopenic dysphagia database (n = 467) to analyze FILS data recorded at admission and after follow-up in 322 cases. A multivariate analysis was performed to determine whether CC and stroke improved the FILS by two points or more., Results: The patient characteristics were as follows: 177 (55%) men; median age, 81 years; median body mass index, 20.3 kg/m 2 ; median CC, 28.2 cm; presence of sarcopenic dysphagia, 183 (56.8%); history of stroke, 103 (32%); median FILS on admission (interquartile range (IQR)), 6 (2-7); and median FILS at the end of the observation (IQR), 7 (7-8). Comparison of FILS at admission and discharge showed that 137 patients had an improvement in the scale of two points or more, whereas 185 patients had no improvement. Multivariate logistic regression analysis showed the factors that were associated independently with an improvement in dysphagia were: age < 80 years (odds ratio (OR) 2.20, 95% confidence interval (CI) 1.36-3.54, p = 0.001); CC ≥ 29.4 cm (OR 2.19, 95% CI 1.33-3.61, p = 0.002); sex (OR 1.67, 95% CI 1.03-2.71, p = 0.037); and stroke (OR 1.85, 95% CI 1.09-3.16, p = 0.023)., Conclusions: Our results suggest that a CC ≥ 29.4 cm and history of stroke contributed to an improvement of inpatient dysphagia at discharge. The contribution of the easy-to-measure CC to predict an improvement in swallowing function may be very useful in daily clinical practice., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders., Methods: A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public., Results: The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP's scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data., Conclusion: The recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation., (© 2021. The Author(s).)

The International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use M9 Guidelines for Biopharmaceutics Classification System Biowaivers reached harmonization in November 2019. However, guidelines for bioequivalence studies are not internationally harmonized, and water as a dissolution medium is only required in Japanese guidelines, regardless of drug solubility. This study investigated the dissolution profiles of generic products in Japan that differ from those of original drugs in dissolution media defined in guidelines. Dissolution profiles disclosed on websites of generic manufacturers were investigated for 262 active ingredients listed in the bluebook (4638 oral solid products listed in the National Health Insurance drug price list) issued by the Ministry of Health, Labour and Welfare. 5% of all generic products were different from the original products in dissolution media, of which 20% was observed in water only. Among the active pharmaceutical ingredients that showed different dissolution profiles only in water, the ratio of original products that showed slower dissolution profiles to the generics was 73%. The ratio of products showing different dissolution in water only was higher than in other media investigated in this study; however, these do not reflect disintegration and dissolution of drug products in the gastrointestinal tract, since bioequivalence has been confirmed in human studies and the generic products were approved by Japanese authorities. Therefore, a discussion about the required use of water as a dissolution medium in the Japanese guidelines is needed among industry, academia, and regulatory authorities., (© 2021. The Drug Information Association, Inc.)