A Descriptive Comparative Analysis of Safety Concerns Outlaid in the Risk Management Plans of the European Union and Japan.

Purpose: This study aimed to obtain a better understanding of the characteristics of the risk management plans (RMP) and the background regulatory policies governing them, in the European Union (EU) and Japan. This was done by descriptively comparing the safety concerns (SCs) listed in the RMP and examining their relationships with product labeling.

Methods: Information regarding SCs was collected from the published RMP of both the EU and Japan for the targeted products-all of which were commonly approved in both regions.

Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval.

Drug lag is a serious issue for patients with life-threatening diseases such as cancer. Japan and Korea have been facing a large drug lag, despite having a large market and a good clinical trial environment. We analyzed drug lags for anticancer drugs between these countries, using the information on 82 anticancer drugs approved in the United States between 2017 and 2022.

Are Exposure Recommendations for QT Evaluation Being Fulfilled?

Pharmaceutical companies have several options to evaluate drug-induced QT prolongation, often referred to as QT pathways, during clinical development. Current regulatory practices recommend achieving high clinical exposure (HCE) for conventional thorough QT (TQT) studies. An alternative to the TQT study, commonly known as the Q&A 5.

Development of a Drug Safety Signal Detection Reference Set Using Japanese Safety Information.

Introduction: One of the main objectives of pharmacovigilance activities is to confirm unknown adverse drug reactions (ADRs), and data-mining methods have been developed to detect signals that are candidates for ADRs. Reference sets have been developed to evaluate the performance of the data-mining methods. However, reference sets generated in previous studies are not based on Japanese safety information; therefore, they are not suitable for use in evaluation studies in Japan because some drugs have not been approved or marketed for a long time in Japan.

Changes in taste and odor sensitivities during repeated bicycle ergometer exercises.

Background: Effective nutritional support is essential for maintaining good performance during exercise. Taste and olfaction are key senses for food intake, and understanding how their sensitivities change during exercise is important for effective nutritional support. However, the effects of exercise on taste and odor sensitivities remain unclear.

Background Factors Contributing to Safety Warning Discordance in the Initial Labeling of New Drugs in Japan, the United States, and the European Union.

Drug labels summarize essential safety information for healthcare professionals and patients. However, studies have reported a discordance of safety information in drug labeling among countries/regions. We aimed to identify the characteristics of adverse events associated with discordant safety warnings during the initial labeling of new drugs approved at approximately the same time in Japan, the United States, and the European Union.

Immune-related and Common Adverse Events With Programmed Cell Death 1/Programmed Cell Death Ligand 1 inhibitors combined with other Anticancer Therapy for Solid Tumors: A Systematic Review and Meta-analysis.

Aims: The combination of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors and anticancer therapies has been in the spotlight in recent years. However, the risks associated with these combination therapies are not fully elucidated. The primary objective of this study was to evaluate the relative risk of organ-specific immune-related adverse events (irAEs) and common adverse events (AEs) in patients treated with PD-1/PD-L1 inhibitor-based combination therapies compared to those treated with PD-1/PD-L1 inhibitor monotherapy for solid tumors.

The complexities of salt taste reception: insights into the role of TMC4 in chloride taste detection.

Although salt is an essential substance vital to life, excessive salt intake could cause various health issues. Therefore, new technologies and strategies should be developed to reduce salt intake without compromising taste. However, the underlying physiological mechanisms of salt taste reception is complex and not completely understood.

Safety Evaluation and Information Provision for Appropriate Drug Usage in Elderly Patients in Japan.

The elderly Japanese population is growing rapidly due to increasing longevity and declining birth rates. These findings have implications for drug development and safety in elderly patients; however, the Japanese stakeholders have been slow to adapt. This study aimed at examining methods for providing sufficient information on safe use of pharmaceuticals in elderly patients in Japan.

New Drug Development Strategy in Japan: Flexibility in Guideline Adherence.

Recently, a new type of drug lag, known as "drug loss" has emerged in Japan. It is a condition where the development of a drug approved in other countries has not been initiated in Japan. For 265 new drugs approved in the United States or Europe during 2010-2020, only 31% had commenced development in Japan as of December 31, 2020.

Paediatric Drug Development in Japan: Current Status and Future Challenges.

Introduction: Until around 2000, the number of medicinal products labelled for paediatric use was limited worldwide. Regulatory measures to promote paediatric drug development in the US and Europe and the establishment of an international guideline (ICH-E11) have led to an increase in the number of paediatric labels. In Japan, efforts have been made to promote the development of paediatric drugs.

Soil volatilomics uncovers tight linkage between soybean presence and soil omics profiles in agricultural fields.

Securing a stable food supply and achieving sustainable agricultural production are essential for mitigating future food insecurity. Soil metabolomics is a promising tool for capturing soil status, which is a critical issue for future sustainable food security. This study aims to provide deeper insights into the status of soybean-grown fields under varying soil conditions over three years by employing comprehensive soil volatile organic compound (VOC) profiling, also known as soil volatilomics.

Changes in gene expression due to aging in the hypothalamus of mice.

Aging generally affects food consumption and energy metabolism. Since the feeding center is located in the hypothalamus, it is a major target for understanding the mechanism of age-related changes in eating behavior and metabolism. To obtain insight into the age-related changes in gene expression in the hypothalamus, we investigated genes whose expression changes with age in the hypothalamus.

Characteristics of Clinical Trials for the US Food and Drug Administration Accelerated Approval and Subsequent Confirmatory Trials: Implications for Drug Approval in Japan.

The Accelerated Approval (AA) Program of the United States (US) Food and Drug Administration (FDA) was established to facilitate and expedite access to new drugs for serious or life-threatening conditions. Although many drugs have granted AAs in the US, the number of approvals under the conditional approval system in Japan remains limited. This study aimed to examine whether confirmatory trials after the US AA are conducted in accordance with the design of postmarketing requirements and assess the timing of regular approval (RA) in Japan for drugs that have been granted US AA.

Factors Associated with Inclusion of Japan in Phase I Multiregional Clinical Trials in Oncology.

Background: Early inclusion of Japan in the global development program could be a key factor in reducing the drug lag, making participation in phase I multiregional clinical trials (Ph. I MRCTs) an important consideration for oncology drug development in Japan. We aimed to investigate the factors associated with the inclusion of Japan in Ph.

A Systematic Review of Treatment-Related Adverse Events for Combination Therapy of Multiple Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor.

Background: Combination therapy with multiple tyrosine kinase inhibitors (multi-TKIs) and immune checkpoint inhibitors (ICIs) has been increasingly tested in clinical studies. This study aimed to investigate the effect of the addition of ICI to multi-TKIs on the profile of treatment-related adverse events.

Methods: An electronic database search was performed using PubMed and Web of Science to identify published clinical studies on multi-TKI monotherapy and multi-TKI plus ICI combination therapy from July 20, 2005 to July 1, 2023.

Aging does not affect the proportion of taste cell types in mice.

Generally, taste sensitivity is known to change with age. However, the molecular mechanisms underlying this phenomenon remain unclear. Mammalian taste buds are classified into type I, II, III, and IV cells; among them, type II and III cells have an important role in the taste detection process.

Characteristics of Anticancer Drugs Approved Under the Accelerated Approval Program in the US: Success or Failure in Converting to Regular Approval.

Background: Accelerated approval (AA) program expedites access to promising drugs for life-threatening conditions, particularly in oncology. However, challenges arise from the trade-off between faster access and the certainty of clinical benefits. We examined the differences between the indications for successful conversion of AA to regular approval (RA) and those withdrawn from the perspective of whether the confirmatory trial was appropriately designed and conducted to verify the efficacy estimated in the pivotal trial for AA (AA trial).

Comparison of the Incidence of Adverse Events Between Japanese and Non-Japanese Healthy Subjects in Phase I Studies: A Systematic Review and Meta-Analysis.

Background And Objective: Ethnic and racial differences are key factors affecting the results of clinical studies. However, the influence of these factors on the efficacy and safety of medicinal products remains unclear. Race-dependent nature is considered to be one of the factors causing differences in clinical findings, and we investigated its influence on the safety evaluation of drugs.

Mouse TMC4 is involved in the detection of chloride taste of salts.

Licking behavior with various salts in transmembrane channel-like 4 (Tmc4) knockout (KO) mice was observed. In Tmc4 KO mice, a significant decrease in sensitivity to chloride salts, such as NaCl, KCl, and NH4Cl, was observed, while no significant decrease in sensitivity to Na-gluconate was observed. This finding suggests that TMC4 may be involved in the detection of chloride taste.

Effect of salivary gland removal on taste preference in mice.

To evaluate the effect of decreased salivary secretion on taste preference, we investigated taste preference for five basic tastes by a 48 h two-bottle preference test using a mouse model (desalivated mice) that underwent surgical removal of three major salivary glands: the parotid, submandibular, and sublingual glands. In the desalivated mice, the avoidance behaviors for bitter and salty tastes and the attractive behaviors for sweet and umami tastes were significantly decreased. We confirmed that saliva is necessary to maintain normal taste preference.

Impact of the US Accelerated Approval for New Anticancer Drugs on Time to Verification of Benefit and Regulatory Approval in the EU and Japan.

The accelerated approval (AA) program in the USA has succeeded in expediting the regulatory approval of new cancer drugs based on surrogate endpoint data. It is unclear whether the AA program promotes overall drug development, including verification of the clinical benefit, as the verification of drugs granted AA often takes long time. To determine the impact of the AA program on overall drug development, the time required for verification of clinical benefits was compared between anticancer drugs that initially received AA and those that received regular approval (RA).

Modeling the structure of the transmembrane domain of T1R3, a subunit of the sweet taste receptor, with neohesperidin dihydrochalcone using molecular dynamics simulation.

Neohesperidin dihydrochalcone (NHDC) is a sweetener, which interacts with the transmembrane domain (TMD) of the T1R3 subunit of the human sweet taste receptor. Although NHDC and a sweet taste inhibitor lactisole share similar structural motifs, they have opposite effects on the receptor. This study involved the creation of an NHDC-docked model of T1R3 TMD through mutational analyses followed by in silico simulations.

Effect of Addition of Umami and Sour Components on NaCl Taste in Humans.

We investigated the effects of adding umami and sour components to the taste characteristics of NaCl (75 mM and 100 mM) using sensory evaluation. Here, we employed a mixture of 1 mM monosodium glutamate (MSG) and 0.5 mM inosine 5'-monophosphate (IMP) as the umami component and 3 mM citric acid as the sour component.