PONE-D-23-28375Changes in the place of death during COVID-19 pandemic in JapanPLOS ONE

Dear Dr. Otsuka,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study addresses a very pertinent and timely issue, especially in the context of global aging and the challenges the COVID-19 pandemic has posed on health systems worldwide.

The findings are of significant importance as they illustrate the changing dynamics of the PoD in Japan, particularly during the pandemic years. The shift from hospital deaths to home deaths, especially in the older population with cancer or old age, is a trend that needs to be comprehensively understood for potential policy implications and healthcare planning. I find this manuscript to be of high quality and relevance. It sheds light on a topic that warrants immediate attention, especially in the current global health scenario.

Reviewer #2: I have reviewed the manuscript titled "Changes in the Place of Death During COVID-19 Pandemic in Japan." While the authors have made an attempt to explore the effects of the COVID-19 pandemic on the location of deaths in Japan, I have several major concerns regarding the methodology and the scientific significance of the study, which need to be addressed before considering publication.

The primary concern is the limited timeframe after COVID-19 pandemic in the study. The COVID-19 pandemic only spanned two years. To effectively evaluate the impact of COVID-19, it is desirable to have data covering both pre-pandemic (2019) and pandemic (2020) periods, with at least five years of data on each side [International Journal of Epidemiology, 2017, 348–355]. The short observation period may introduce bias, making it challenging to draw robust conclusions about the impact of COVID-19 on the changes observed. Furthermore, while the results may indicate APC, it is essential to consider whether these changes are clinically significant and meaningful absolute difference in the context of a 70-year timeframe.

The manuscript reports changes in the place of death, particularly an increase in home deaths due to cancer and old age. However, it lacks an in-depth analysis of the underlying reasons for these changes. A significant portion of the discussion relies on findings from other studies, which may not directly correlate with the data presented in this study. The discussion, therefore, appears to be speculative and lacking a scientific foundation.

The clinical implications of the study's findings remain unclear. It is challenging to ascertain what actionable insights or recommendations can be derived from this research, especially for future pandemic.

Reviewer #3: The paper analyzes the variation in the place of death (PoD) according to major causes of death during the COVID-19 pandemic in Japan using nationwide death certificate data. The results are interesting and contribute to the analysis of the effect of the pandemic on general and cause-specific mortality. The paper is well written and the results are clearly described. However, some clarifications in the methods section and some revisions of the results would improve the paper.

My comments and suggestions for the authors:

Materials and Methods

1) Line 73. Since the analysis concerns also cause-specific mortality data a more detailed description of death certificates data processing is required. In particular, specify whether death certificates are entirely processed through an automatic coding system (for the coding of the single entries and the selection of the underlying cause) or they are in part manually reviewed by experts (in this case, please report the percentage of certificates manually reviewed). In addition, since you are investigating long-time series data, you should specify whether the same coding system was adopted all over the study period, and whether there have been any change/update in the classification of causes of death (for example from ICD9 to ICD10). Lastly, it should specified that the analysis refers to underlying cause-of-death data (I suppose so).

2) Line 84, Statistical analysis. Please add details on the Jointpoint regression analysis, for instance minimum/maximum number of joinpoints tested, model used and regressor (calendar year). In addition, as some readers might not be familiar with this kind of analysis, I recommend to explain that the APC indicates the annual percent change in the proportion (?) of deaths by PoD and that it has been estimated for different time periods.

Results

3) Lines 100-101: “Trends in the number of PoDs over the past 70 years in Japan are presented in Fig. 1. Since the 1950s, hospital deaths have steadily increased, whereas home deaths have gradually declined”. From Fig.1 I would say that home deaths have gradually declined until mid 2000s, being gradually increasing thereafter.

4) lines 100-104: Please cite in the text the proportion of deaths by each single PoD on total deaths at the beginning and at the end of the study period. I would also suggest to include a table (in the main text or in the supplementary material) reporting the frequencies of deaths by PoD and their proportion in each age stratum, for the first year and the last year considered in the analysis i.e. 2001 and 2021 (see a proposal below), and to briefly comment on them before the presentation of the results of the joinpoint analysis.

2001 2021

no. of deaths % no. of deaths %

0-19 yrs

home

hospital

nursing home

20-64 yrs

home

hospital

nursing home

≥65 yrs

home

hospital

nursing home

5) Lines 111-112: “In order to detect the impact of COVID-19 more sensitively, the results of the trend analysis of the proportion of PoDs focused on the last 20 years in the 21st century”. This sentence expresses a methodological choice, therefore it should be moved to the methods section (Statistical analysis).

6) line 118: “ hospital deaths decreased suddenly in 2019…” it would be more appropriate to say “from 2019 to 2021” than “in 2019”

7) How much do the top five causes of death account on total mortality in Japan? This proportion should be explicitly mentioned in the text

Discussion

The change in time-trends of home deaths due to cancer or old age among the elderly population from 2019 is the main finding of the study.

8) Could the increase in home deaths due to old age be in part attributable to the possible under-diagnosis of SARS-CoV-2 infection, especially during the early pandemic phase? This aspect should be briefly discussed

9) I think the analysis of results could benefit from a brief description of the pandemic phases in Japan during 2020 and 2021

10) In the assessment of time-trends (in particular the increase in home/nursing home deaths) did you evaluate also the possible role of population aging? Although this effect is expected to be limited, this aspect should be discussed

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Reviewer #1: No

Reviewer #2: Yes: Hiroyuki Ohbe

Reviewer #3: No

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Changes in the place of death before and during the COVID-19 pandemic in Japan

PONE-D-23-28375R1

Dear Dr. Otsuka,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Mihajlo Jakovljevic, MD, PhD, MAE

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: The authors have properly addressed the comments and they have revised the manuscript accordingly.

The paper has improved and I suggest to accept it for publication

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

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