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Population-Based Observational Study of Adverse Drug Event-Related Mortality in the Super-Aged Society of Japan

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Abstract

Introduction

Adverse drug events (ADEs) are a major cause of mortality.

Objective

We examined long-term trends for ADE-related deaths in Japan.

Methods

This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC).

Results

In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4–4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2–7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period.

Conclusions

The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

Plain Language Summary

Adverse drug events (ADEs) are a public health issue, but descriptive data on ADEs in Japan are limited. Studies have shown that elderly people have a higher risk of dying from ADEs. Japan has one of the most rapidly aging populations and the highest percentage of older individuals worldwide. Clarifying long-term data trends in Japan is important in the aging world. Here, we aimed to clarify the trend in mortality related to ADEs in Japan. We selected 16,417 deaths that were assigned an underlying cause (i.e., ADEs) in vital statistics based on codes from the International Classification of Diseases, Tenth Revision (ICD-10). The crude mortality rate for both sexes increased from 0.44 per 100,000 in 1999 to 1.01 in 2016. The average annual percentage change (average APC), which numerically shows the change over time, was 5.7% throughout the study period. The age-standardised mortality rate, using the population in the first year, increased from 0.44 per 100,000 in 1999 to 0.64 in 2016. The average APC of the age-standardised mortality rate showed an increasing trend at 2.8%. Even after age standardisation, ADE-associated death showed an increasing trend. In particular, population groups aged ≥65 years showed a continuous increasing trend. These findings suggest that the ADE-related mortality rate in Japan is increasing, especially in elderly individuals.

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Acknowledgements

The authors thank Editage (www.editage.jp) for English language editing.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Biomedicine, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 1-1- Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan

    Tomoko Funahashi & Mitsunobu R. Kano

  2. Department of Pharmaceutical Biomedicine, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan

    Toshihiro Koyama & Syunya Iinuma

  3. Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Hideharu Hagiya & Ko Harada

  4. Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Soichiro Ushio & Toshiaki Sendo

  5. Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-1815 Kuramoto, Tokushima, 770-8503, Japan

    Yoshito Zamami, Takahiro Niimura & Keisuke Ishizawa

  6. Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji Yamashiro-cho, Tokushima, 770-8514, Japan

    Kazuaki Shinomiya

  7. Department of Biostatistics, Sapporo Medical University, South 1, West 17, Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan

    Shiro Hinotsu

Authors
  1. Tomoko Funahashi
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  2. Toshihiro Koyama
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  3. Hideharu Hagiya
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  4. Ko Harada
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  6. Soichiro Ushio
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  7. Yoshito Zamami
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  8. Takahiro Niimura
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  9. Kazuaki Shinomiya
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  10. Keisuke Ishizawa
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  11. Toshiaki Sendo
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  12. Shiro Hinotsu
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  13. Mitsunobu R. Kano
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Corresponding author

Correspondence to Toshihiro Koyama.

Ethics declarations

Funding

This study was funded by the Japan Society for the Promotion of Science KAKENHI (19K10533) (Tokyo, Japan).

Conflict of interest

Tomoko Funahashi, Toshihiro Koyama, Hideharu Hagiya, Ko Harada, Syunya Iinuma, Soichiro Ushio, Yoshito Zamami, Takahiro Niimura, Kazuaki Shinomiya, Keisuke Ishizawa, Toshiaki Sendo, Shiro Hinotsu, and Mitsunobu R. Kano have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for Publication

Not applicable.

Availability of data and material

Japanese death certificate data used in the study are available at https://www.e-stat.go.jp/en/statsearch/files?page=1\&toukei=00450011\&tstat=000001028897. All data generated or analysed during this study are included in this published article and its supplementary data files.

Code availability

Joinpoint Regression Program, version 4.8.0.1, April 2020 (Statistical Research and Applications Branch, National Cancer Institute, USA). Microsoft Excel® 2013 (Microsoft Corporation, Redmond, WA, USA).

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Tomoko Funahashi, Shunya Iinuma, Ko Harada, Hideharu Hagiya, and Toshihiro Koyama. The first draft of the manuscript was written by Tomoko Funahashi, Shunya Iinuma, Ko Harada, Hideharu Hagiya, and Toshihiro Koyama. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Funahashi, T., Koyama, T., Hagiya, H. et al. Population-Based Observational Study of Adverse Drug Event-Related Mortality in the Super-Aged Society of Japan. Drug Saf 44, 531–539 (2021). https://doi.org/10.1007/s40264-020-01037-9

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  • DOI: https://doi.org/10.1007/s40264-020-01037-9

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