Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics
Online ISSN : 1882-8272
Print ISSN : 0388-1601
ISSN-L : 0388-1601
Volume 49, Issue 1
Displaying 1-7 of 7 articles from this issue
Short Communication
  • Sachiko TAKENOSHITA-NAKAYA, Yuko TAKEBA, Yuki OHTA, Masanori OOTAKI, M ...
    2018 Volume 49 Issue 1 Pages 3-6
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    Cytochrome P450 (CYP) enzymes contribute to the first-pass metabolism of orally administered drugs in both the liver and human small intestine, thus influencing their bioavailability. Although the CYPs profile in the small intestine of Caucasians was reported previously, that of the Japanese population has not. We investigated CYP (1A2, 2C9, 2C19, 2D6, 3A4 and 3A5) mRNA levels and localization in the small intestine of Japanese. Localization of CYP protein secretion was observed by immunohistochemistry. CYP mRNA levels were analyzed using real-time reverse transcriptase polymerase chain reaction. In the small intestine of Japanese, CYP3A4 and CYP2C19 were the major and second most highly expressed components among these CYPs, present in 63.2% and 21.3% of our subjects, respectively. Our results showed differences between Japanese and Caucasians in the CYP profiles in the small intestine. Respective CYP isozymes in the Japanese small intestine indicate the possibility of influencing first-pass metabolism or drug interactions.

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Forum
  • Toshiko MIYAMOTO, Akiyo AKAISHI, Tomoko TAKAGAI, Kikue KIDA, Masashi A ...
    2018 Volume 49 Issue 1 Pages 7-11
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    Background and objectives: In Japan, the contribution of clinical research coordinators to trials for drug approval is now well recognized in investigators. In 2013, we initiated a clinical research coordinator hospital certification course at our facility. The purpose of the course is to pre-educate medical staff who are candidates for future roles of clinical research coordinator, and to spread recognition of clinical research.

    Methods: To obtain information from course participants, we conducted a qualitative study in 2014, using a focus group interview in six participants who had completed the course in 2013. The initial topic was perceptions of the course before and after participation. Other topics were the present status and issues in clinical research coordinators.

    Results: All participants agreed that the course was acceptable and effective in reexamining their own work and roles from the aspects of clinical research, and that the role of clinical research coordinator itself is not very familiar among staff in the facility. Some participants indicated that even their more senior coworkers have limited recognition about clinical research coordinators.

    Conclusion: There are few reports that deal with awareness-spreading activities that targeted facility staff in positions other than those related to clinical research. This type of education could be considered to more quickly build support of clinical research.

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Original Article
  • Fumio KOJIMA, Toko SHIMOMUKAI, Masanori YOSHIHARA, Hiroaki SHAKUDO, Ka ...
    2018 Volume 49 Issue 1 Pages 15-21
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    We investigated whether the basic concepts of ICH guideline Q8 “ Pharmaceutical Development” relating to the effective and efficient control of quality in drug development can be applied as a means for the effective and efficient implementation of audits carried out as a part of the quality assurance program for clinical trials in clinical development. We divided the clinical trial into 12 processes. Pharmaceuticals and Medical Devices Agency (PMDA) Inquiries from GCP On-site Inspections and Document-based Conformity Inspections, obtained from the PMDA on the basis of the information disclosure system, were categorized into the 12 processes. As our analysis targets, we chose the “ Revision of written informed consent form with regard to serious adverse events (SAEs)” process, which relates to patient safety, and the “ Examination/Observation/Assessment” process, which generates the highest number of inquiries. These two processes were further divided into several sub-processes. The inquiries were analyzed to tabulate the number of harms in each sub-process and to identify the nature of those events. We then identified the process parameters (PPs) of each process as well as deviations from said PPs (hazards), and tabulated the number of these incidences. We found that the number of harms attributable to said two processes were localized in specific sub-processes. Localization was likewise observed in the nature of the harms, the PPs relating to said harms, and deviations from said PPs. We also identified which sub-processes, the nature of harms,the PPs relating to said harms, and deviations from said PPs require management. Our findings suggest that the basic concepts of the ICH-Q8 guidelines can be applied to the quality assurance programs for clinical trials for the effective and efficient implementation of audits.

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  • Mami IWASAKI, Masayuki KANEKO, Mamoru NARUKAWA
    2018 Volume 49 Issue 1 Pages 23-34
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    The risk management plan (RMP) system was introduced in Japan in 2013, to enhance the planning and implementation of pharmacovigilance and risk-minimization activities for new drugs. This system often requires additional pharmacovigilance activities. This study was conducted to discuss effective implementation of pharmacovigilance activities aiming to further improve the safety measures for new drugs in Japan. We investigated the RMPs for 19 new active substances approved in 2013 and 2014 both in Japan and Europe, and compared the safety concerns and pharmacovigilance activities for these drugs in Japan and Europe. The safety concerns were not necessarily the same in Europe and Japan, and the total number of safety concerns in Europe was approximately 1.5 times of that in Japan. In Europe, diverse additional pharmacovigilance activities were planned, and additional pharmacovigilance activities were conducted for approximately 40% of all safety concerns, and for around 30% of all known (identified) safety concerns. In Japan, in contrast, additional pharmacovigilance activities were implemented for 80% of all safety concerns, and for 90% of known safety concerns. Our results suggest that it would be possible to collect safety information adequately from a wide range of perspectives in Japan through (1) identifying safety concerns by predicting how the drug product will be used in the clinical setting, (2) positioning and conducting various types of research as additional pharmacovigilance activities, and (3) evaluating whether there are real needs for additional pharmacovigilance activities, and additional pharmacovigilance activities should not be conducted for those safety concerns where additional information can be collected from just routine pharmacovigilance activities.

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Short Communication
  • Masao KOBAYAKAWA, Mari TERADA, Hiroshi OHTSU, Kazuo IZUMI, Sho SAITO, ...
    2018 Volume 49 Issue 1 Pages 35-38
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    On 2 May 2017, NIH has released the “NIH and FDA Release Protocol Template for Phase 2 and 3 IND/IDE Clinical Trials” mainly for NIH and FDA funded Clinical Trials. We are now translating this template into Japanese for the improvement of research quality and integrity. We are also comparing the template with the Japanese Ethical Guidelines for Clinical Research Involving Humans. In this article, we would like to give a brief overview of our work. The template is consisted of 11 sections, each divided into several sub-sections. We have compared each section/sub-section with the information to be included in the protocol, as described in the Japanese Ethical Guideline. One of the feature is that there is a “Statement of Compliance” section at the beginning of the template to ensure that the researchers will conduct the trial following the basic premise, such as the accordance to ICH-GCP, Protocol and Informed Consent Form are reviewed by IRB prior to conduct of the trial, and so on. Also, the template guides to write the study procedures in detail, whereas the Japanese Guideline has not described in detail what information should be included within the study procedures. While on the other hand, there are some information the Japanese Guideline is mandating despite the stipulation of ICH-GCP : PI's contact information and available payment and compensation for the subjects. This information varies from site to site, as a consequence, each site is developing its own protocol for the same multi-center trial. This must be one of the topic to be discussed further ; how to distinctly write the mutual information and site-specific information.

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Forum
  • Taeko ISONO, Tetsuji SANUKI, Tsutomu NISHIMURA
    2018 Volume 49 Issue 1 Pages 39-42
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    The purpose of this paper is to describe problems encountered in the course of conducting a government-funded inaugural investigator-initiated clinical trial in the Department of Otolaryngology-Head and Neck Surgery at Kumamoto University Hospital. A principal area of difficulty involved the process of executing contracts between the hospital and various clinical research organizations (CRO). As government funds were disbursed year by year, the budget office of the university hospital required annual budgets, rather than allowing for a single budget encompassing the 3 years of the trail, which would have enabled us to make multi-year contracts with each CRO. While the function of each CRO was clearly established, it was exceedingly difficult to estimate exact timing of services rendered by a given CRO in order to calculate the percentage of work to be accomplished in a given year. As one function of some CROs was to provide data, it was possible for a fiscal year to close without any visible product. The university hospital had difficulty understanding the reality of the situation. In addition, as the government required an open bidding process for contracts with CRO's, this annual process resulted in excessive expenditure of resources. Being the first clinical trial performed by our department, as well as at the university hospital, significant time and energy had to be devoted to developing protocol and establishing a working framework for the trials to take place. Staff members of the university contract office were generally unaware of standard procedures for clinical trials, requiring considerable explanation.

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  • Keiichiro YAMAMOTO, Kenji MATSUI, Shimon TASHIRO, Tomohide IBUKI
    2018 Volume 49 Issue 1 Pages 43-49
    Published: January 31, 2018
    Released on J-STAGE: February 23, 2018
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    The debate over an ethically appropriate way to handle incidental findings―whether researchers or clinicians should bear some duty to offer back such findings to research participants or patients―has also been the focus of attention in Japanese genomic research and medicine since the introduction of next generation sequencing. Those who engage in the debate in Japan, where one can see the strong influence of the American College of Medical Genetics and Genomics (ACMG) policy statement in 2013, tend to understand incidental findings in terms of the primary or the non-primary. In this classification, secondary findings as well as incidental findings fall into the latter category. Given the complicated discussion over the very concept of “incidental findings” in the West, this classification may still be intelligible but inconclusive. According to Presidential Commission for the Study of Bioethical Issues in 2013 and ACMG SF v2.0 in 2016, the most crucial distinction from an ethical point of view appears to be made by the concept of intention : both primary findings and secondary findings can be said to be intentionally sought, whereas incidental findings, whether anticipatable or unanticipatable, cannot. Thus, we can regard incidental findings as unintentional ones. This paper aims to propose a more appropriate classification method based on the concept of intention, with philosophical and ethical arguments for it, clarify the terminological or conceptual confusions which can be seen in Japan, and introduce a better term and its definition to express incidental findings in Japanese.

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