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International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries

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Abstract

Background and Objective

Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level.

Methods

This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates.

Results

The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92–3.18) in 2001 to 6.86 (95% confidence interval 5.76–7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20–50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019.

Conclusions

The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally.

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Acknowledgements

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

Author information

Authors and Affiliations

  1. Department of Health Data Science, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Toshihiro Koyama, Shunya Iinuma, Yuka Osaki & Sayoko Nishimura

  2. Graduate School of Human Sciences, Osaka University, Osaka, Japan

    Michio Yamamoto

  3. RIKEN Center for Advanced Intelligence Project, Tokyo, Japan

    Michio Yamamoto

  4. Department of Clinical Pharmacology and Therapeutics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Takahiro Niimura

  5. Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY, USA

    Ko Harada

  6. Department of Pharmacy, Okayama University Hospital, Okayama, Japan

    Yoshito Zamami

  7. Department of Infectious Diseases, Okayama University Hospital, Okayama, 7008558, Japan

    Hideharu Hagiya

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  1. Toshihiro Koyama
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Corresponding author

Correspondence to Hideharu Hagiya.

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Funding

This work was supported by the Japan Society for the Promotion of Science (KAKENHI Grant No. 22K10415). The sponsors had no role in the study design; in the collection, analysis and interpretation of the data; in the writing of the manuscript; and in the decision to submit the article for publication. All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity and accuracy of the data.

Conflict of interest

Toshihiro Koyama, Shunya Iinuma, Michio Yamamoto, Takahiro Niimura, Yuka Osaki, Sayoko Nishimura, Ko Harada, Yoshito Zamami and Hideharu Hagiya have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This study was approved by the Institutional Review Board of Okayama University Hospital (no. 2007-011) and performed following the Declaration of Helsinki. The requirement for informed consent was waived because of the retrospective nature and analysis of routinely collected data. Reporting of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.

Consent to participate

Not applicable.

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Not applicable.

Availability of data and material

The datasets generated and analysed during the current study are available from the corresponding author upon reasonable request. The corresponding author has full access to all the study data and takes final responsibility for the decision to submit this work for publication.

Code availability

The ICD-10 codes used in the study are provided as ESM.

Author contributions

TK conceived the study; TK, HH and SI designed the study and wrote the manuscript. TK, MY and SI performed the statistical analysis. TK, SI and TN performed the data processing. All authors interpreted the results and critiqued the manuscript. All authors gave final approval for publication of the manuscript.

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Koyama, T., Iinuma, S., Yamamoto, M. et al. International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries. Drug Saf 47, 237–249 (2024). https://doi.org/10.1007/s40264-023-01387-0

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