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Utilisation of Human Pharmacology Studies with Biomarkers for New Drug Applications in Japan

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Abstract

Objective:This study evaluated the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation conducted for new drug applications (NDAs) submitted to the Japanese regulatory authority, the Ministry of Health, Labour and Welfare (MHLW).

Methods: A total of 50 new chemical entities (NCEs) posted on the Websites, which were approved from June 2000 to November 2001, were evaluated by investigating their approval information. The utilisation of human pharmacology studies with biomarkers was evaluated by focusing on the classification referred to biomarkers for either efficacy or safety estimation and timing of studies.

Results: The human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted in 20 compounds classified by utilising measures of either efficacy (17 compounds) or safety (seven compounds). In 4 of 17 NCEs, some of the biomarkers in human pharmacology studies were similar to the clinical endpoints for efficacy assessment in therapeutic exploratory and/or therapeutic confirmatory studies. For safety assessment in therapeutic exploratory and/or therapeutic confirmatory studies, clinical endpoints rather than biomarkers in human pharmacology studies were used in all seven NCEs. The timing of each type of clinical study could only be obtained for 15 NCEs. Of these 15 NCEs, human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted on six compounds. There were only two compounds for which human pharmacology studies with biomarkers for efficacy estimation were conducted before pivotal studies such as a therapeutic exploratory study or a bridging study.

Conclusion: Our survey suggests that with Japanese NDAs, human pharmacology studies with biomarkers for either efficacy or safety estimation do not play a key role in accelerating drug development and maximising the knowledge gained from confirmatory trials. The relationship between a biomarker and a clinical endpoint should be investigated appropriately for accelerating drug development. We think that the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation in the regulatory review process for NDAs should be encouraged with the advancements of drug evaluation research using an appropriate biomarker based on clinical pharmacology.

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Acknowledgements

The opinions and views expressed in this article are those of the authors and not of the Ministry of Health, Labour and Welfare in Japan. No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Laboratory of Bio-Pharmaceutics, Faculty of Pharmaceutical Sciences, Josai International University, Togane, Chiba, 283-8555, Japan

    Yasuo Kodama & Mizue Mutoh

  2. Department of Clinical Pharmacology, Division of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan

    Kazuyuki Saito & Akio Fujimura

  3. Graduate School of Pharmaceutical Sciences, The University of Kanazawa, Kanazawa, Japan

    Shunsuke Ono

  4. Department of Pharmacy, The University of Miyazaki, Miyazaki, Japan

    Hirofumi Kodama

  5. Department of Clinical Pharmacy, The University of Oita, Oita, Japan

    Masae Kuranari

  6. Department of Clinical Pharmacology and Therapeutics, The University of Oita, Oita, Japan

    Kimiko Tsutsumi

  7. Pharmaceuticals and Medical Devices Evaluation Center, National Institute of Health Sciences, Ministry of Health, Labour and Welfare, Tokyo, Japan

    Deborah F. Yaplee & Hiromi Takano-Ohmuro

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  1. Yasuo Kodama
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  2. Kazuyuki Saito
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  3. Shunsuke Ono
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  4. Hirofumi Kodama
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  6. Kimiko Tsutsumi
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  7. Deborah F. Yaplee
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  8. Hiromi Takano-Ohmuro
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  9. Mizue Mutoh
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  10. Akio Fujimura
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Correspondence to Yasuo Kodama.

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Kodama, Y., Saito, K., Ono, S. et al. Utilisation of Human Pharmacology Studies with Biomarkers for New Drug Applications in Japan. Drugs in R D 6, 21–34 (2005). https://doi.org/10.2165/00126839-200506010-00003

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  • DOI: https://doi.org/10.2165/00126839-200506010-00003

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