Background: Tumor necrosis factor (TNF) blockers are highly effective in RA treatment, have been used widely for rheumatoid arthritis (RA) therapy worldwide, and can result in remission in combination with other disease-modifying antirheumatic drugs. However, it was reported that there are large interindividual differences in therapeutic responses to TNF blockers. In addition, there are few studies comparing ethnic and gender differences in allele frequencies of TNF-α polymorphisms. To obtain fundamental information for the establishment of personalized pharmacotherapy with TNF blockers, we investigated allele and genotype frequencies and gender differences in TNF-α polymorphisms among healthy Japanese adults and RA patients, and ethnic differences by comparing literature data.
Methods: We genotyped 292 healthy Japanese adults and 153 Japanese RA patients for TNF-α polymorphisms (TNF −238G >A, −308G>A, −857C>T) using the polymerase chain reaction method. Pearson's chi-square test was used to compare the allele and genotype frequencies of TNF-α polymorphisms among gender and ethnic groups.
Results: In healthy Japanese adults and RA patients, there were no associations between TNF-α genotypes and gender differences. However, we found a significant difference in the allele and genotype frequencies of TNF-α −308G>A and −857C>T between a Japanese population and Caucasians.
Conclusion: The study showed a significant difference in the allele and genotype frequencies of TNF-α −308G>A and −857C>T between a Japanese population and Caucasians, but there were no associations between TNF-α genotypes and gender differences in healthy Japanese adults and RA patients. Further study is necessary to investigate these associations in clinical studies whether the differences in allelic frequencies in ethnic groups contribute to the variations in response and toxicity of TNF blockers.
The aim of this study was to evaluate drug release from a bisoprolol patch preparation containing 4 mg bisoprolol and its pharmacokinetics after an 8-h application. The residual drug in the preparation and the pharmacokinetics after removing the preparation were monitored in healthy voluneers and patients. In the first study, 11 volunteers were enrolled and the patch was applied for 8h. In the second study, 8 patients were enrolled and the patch was applied once daily for 24h. The amount of residual bisoprolol in the patch and serum concentration of bisoprolol were determined by high-performance liquid chromatography. Percentage of drug release from the patch was 82.6±8.1% in volunteers and 89.4±5.5% in patients, with no significant difference between two groups. Percentage of drug release in patients was similar to the value given in the drug interview form (88.3±3.7%). No difference in the time of reaching maximum drug concentration (Tmax) was abserved between volunteers and the interview form data (10.9±1.6h vs. 10.0±2.1h), but the maximum drug concentration ( Cmax) and elimination half-life (T1/ 2) were slightly lower in volunteers than in the interview form data (Cmax : 5.3±3.2 ng/mL vs. 6.5±2.5 ng/mL,T1/ 2 : 13.7±2.7h vs. 15.0±2.7h). These results suggest that there are no differences in drug release and pharmacokinetics of the bisoprolol patch preparation when the patch preparation was applied for 8 and for 24h.
Clinical trials are a crucial step in the development of new medical technologies. Obtaining informed consent (IC) is a key component of clinical trials, which ensures that potential participants have the necessary information for decision-making. While patients' involvement is essential to improve the systems and circumstances of clinical trials, their perspectives and experiences are rarely shared with others. This study aims to investigate patients' perspectives and experiences of IC in clinical trials in Japan. A mixed method approach was adopted, including an internet-based survey of 21,502 patients and in-depth interviews of 41 patients. In the survey, 12,506 responses were analyzed, focusing on patients' understanding of IC. Among the 12,506 patients, 2,320 had some experience of clinical trials. Among the 888 patients who remembered receiving an explanation from the medical staff, 93.6% responded that it was easy to understand. Most respondents (84.5%) who had received an IC form read it again and 54.5% did not spend much time thinking before deciding whether to participate. From the in-depth interviews, we identified the following: the timing of decision-making and the meaning of IC for the patients. The patients made their “informal” decision prior to the “formal” IC process. They confirmed their “informal” decision during the IC process by collecting important information regarding the health risk of participation. From the patients' perspective, the timing of decision-making is outside the IC process. While patients make an informal decision, both medical staff and patients should recognize that written consent is the formal decision.
Background: Many surveys on perception changes in clinical trial participants have been conducted. However, these surveys have provided only qualitative evaluations of the impressions in participating in clinical trials. The degree of perception changes in participants during clinical trials and the factors that contribute to perception changes remain unclear.
Objective: Understanding the perceptions of participants is extremely important to promote clinical trials. The aims of this study were to clarify quantitatively the degree of perception changes in participants during clinical trials and to identify the factors contributing to the changes.
Methods: We surveyed perception changes in the same participants before and after clinical trials. The degree of anxiety towards clinical trials was determined using the Visual Analog Scale (VAS). The factors contributing to perception changes in participants were also analyzed.
Results: Participants expected positive therapeutic effects, but also had a vague sense of anxiety prior to clinical trials. The mean VAS score for anxiety was 46.7 mm before clinical trials and decreased significantly to 38.0 mm after clinical trial (P＝0.002). Factors that contributed to perception changes by participants included the effectiveness of the investigational drug for individual trial participant and constraint of clinical trial schedule. In addition, the management of clinical research coordinators (CRC) was highly evaluated by participants.
Conclusion: These results suggested that CRC should contribute to the promotion of clinical trials by supporting participants who feel anxious and proposing treatment methods that reduce burden on participants to clinical trial sponsors.
Proceedings of the 23rd Training Course in Clinical Pharmacology and Therapeutics“Safety of Pharmacotherapy”