Background: Liver dysfunction is one factor that affects the pharmacokinetics of voriconazole (VRCZ). Evaluation of liver function may thus be useful for setting the initial VRCZ dosage. Recently, the albumin-bilirubin (ALBI) score has been developed as a new model to assess liver function in liver disease. We explored the association between ALBI score and the incidence of plasma VRCZ concentrations ≥ 4 µg/mL during VRCZ administration in patients treated for hematological malignancies.

Methods: We enrolled 79 patients (mean age, 67.8 years; 58 men) admitted to our hospital for treatment of hematological malignancies who received oral VRCZ loading doses. The following data were recorded: sex, age, weight, height, VRCZ maintenance dose per body weight, and laboratory data including plasma drug concentrations on day 4 after starting VRCZ administration. The primary outcome was the incidence of plasma drug concentrations ≥ 4 µg/mL on day 4 of VRCZ administration.

Results: Among 79 patients analyzed for VRCZ plasma concentrations, 43 (54.4%) had plasma drug concentrations ≥4 µg/mL on day 4 of VRCZ administration. The incidence of plasma drug concentration ≥ 4 µg/mL on day 4 of VRCZ administration was significantly higher in patients with an ALBI score ≥−2.27 (83.0%) than in patients with an ALBI score <−2.27 (12.5%; P < 0.001). Multivariate analysis revealed that ALBI score (odds ratio 56.716, 95% confidence interval 6.659-483.0; P < 0.001) was independently associated with the incidence of plasma drug concentrations ≥ 4 µg/mL on day 4 of VRCZ administration.

Conclusions: ALBI score was superior for distinguishing the occurrence of high plasma drug concentrations (≥ 4 µg/mL) early in treatment in patients receiving VRCZ loading dose therapy. ALBI score may offer a better indicator for determining a safe initial VRCZ dose for patients undergoing treatment for hematological malignancies.

In order to acquire foundational data aimed at enhancing support for practical cancer research, a questionnaire-based survey of the Practical Research for Innovative Cancer Control Management Office (PRIMO) was distributed to the principal and subprincipal investigators of the Practical Research for Innovative Cancer Control of the Japan Agency for Medical Research and Development between June 20 and July 8, 2024. A total of 165 researchers responded, 70.3% of whom knew about PRIMO’s research support. Clinical research was of interest to 50.3% of the respondents, and many expected to utilize PRIMO consultations in their exit-strategy studies. In terms of Technical Support Schemes, utilization of the National Cancer Center Biobank attracted the most attention, with 38.8% of respondents expressing interest. The Cancer Treatment Development Charts published on the website were viewed by 33% of respondents, with the most common purpose being to understand trends in clinical research. The Cancer Treatment Development Chart categories of interest, in order, included adult solid, pediatric solid, and pediatric hematologic tumors. The results of this study highlight the addressal of cancer research support needs by PRIMO, including needs associated with practical application research. Many researchers were aware of the issues indicated in "The National Comprehensive 10-year Strategy for Cancer Control." Surveys aimed at researchers can be used to clearly identify specific needs in terms of research support, with the responses being used to expand support systems that promote research and development.

Objective: The treatment of rheumatoid arthritis (RA) in Japan has evolved significantly since the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) in 2003. This study aimed to identify the key factors associated with poor drug continuation among patients with RA.

Methods: Using the JMDC prescription database, we analyzed the utilization of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Japan. Patient characteristics were compared between those who continued treatment for 2 years and those who discontinued treatment to identify the factors contributing to poor continuation.

Results: A total of 1,890 patients (mean age: 49 years; female: 76.2%) were included in the study. The baseline corticosteroid co-administration rate was 47% (535/1,131) in the continuation group and 58% (444/759) in the discontinuation group (p<0.0001). Fracture history was higher among those who discontinued treatment (3.2% vs. 1.8%, p＝0.049). Independent factors for continuation included corticosteroid use (odds ratio [OR]: 0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001), fracture history (OR: 0.53; 95% CI: 0.29-0.97, p＝0.039), and male sex (OR: 1.32; 95% CI: 1.06-1.64, p＝0.014).

Conclusion: This study identified corticosteroid use and male sex as independent factors contributing to poor continuation of b/tsDMARDs among Japanese patients with RA within 2 years of treatment initiation. The history of fracture was also associated with poor continuation; however, given its low prevalence and wide confidence interval, this finding should be regarded as exploratory.

The Single Institutional Review Board (IRB) has been promoted to enhance the efficiency of clinical trials in Japan. However, studies clarifying the extent of use, challenges, and pros and cons of Single IRB systems within Japanese medical institutions are lacking. Therefore, we conducted a questionnaire survey targeting Advanced Treatment Hospital to address these issues. The results revealed that external IRBs were not widely used by the institutions. Some institutions identified the potential advantages of allowing sponsors to request direct review by a Single IRB. However, concerns were also raised, which included difficulties in responding to institution-specific issues, reduced revenue from IRB review fees, and increased administrative burden due to coordination with external IRBs. Addressing the increased burden associated with a Single IRB aligns with the goals of the “2025 Clinical Trial Ecosystem Implementation Promotion Project” led by the Pharmaceuticals and Medical Devices Agency. The 2025 edition of the “Future Direction for the Promotion of Clinical Trials and Studies,” published by the Ministry of Health, Labor, and Welfare, also highlights the need to ensure the quality of IRBs. These findings suggest that future discussions on Single IRB implementation are warranted. All stakeholders should collaborate to establish a Single IRB system that minimizes the burden on medical institutions to promote clinical trials in Japan.

Background: The definition and proper use of the “Note to File” (NTF) in clinical trials are ambiguous in Japan, leading to inconsistent application. While the use of NTFs is increasing, their overuse is a concern.

Objective: This study analyzes the challenges of NTF use, triggered by a case example in an investigator-initiated trial, to identify issues in current domestic and international practices, and aims to propose standardized handling of NTFs.

Methods: We reviewed global NTF definitions and usage, then analyzed NTF application in 325 clinical trials conducted at our hospital.

Results & Discussion: Internationally, NTFs are used to document root causes and corrective actions for irregular incidents. In Japan, they primarily function as supplementary records and were frequently used for operational and case record supplements. The lack of a standardized NTF format results in content variability and, in some cases, even includes critical issues that should have been addressed through formal processes.

Conclusion: We propose implementing standardized NTF formats and guidelines to ensure clear documentation of problems, causes, and resolutions. This is expected to improve the consistency and quality of clinical trial documentation.