PONE-D-22-24580JOINT MODELING OF LONGITUDINAL CHANGE IN PULSE RATE AND SURVIVAL TIME OF HEART FAILURE PATIENTS TREATED AT ARBAMINCH GENERAL HOSPITAL, SOUTHERN ETHIOPIAPLOS ONE

Dear Dr. Anjullo,

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Kind regards,

Jaimin R. Trivedi, MBBS, MPH

Academic Editor

PLOS ONE

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2. Please amend your current ethics statement to address the following concerns:

a) Did participants provide their written or verbal informed consent to participate in this study?

b) If consent was verbal, please explain i) why written consent was not obtained, ii) how you documented participant consent, and iii) whether the ethics committees/IRB approved this consent procedure.

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We will update your Data Availability statement on your behalf to reflect the information you provide.

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5. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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: Yes

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

Reviewer #1: Yes

Reviewer #2: 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: No

Reviewer #2: Yes

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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: No

Reviewer #2: 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: This is a well written study. The results section needs to be abit more clear and emphasis to be made on percentages rather than frequencies. This can be re-written to make sure its reader friendly. Also, for the graphs, they need to be higher resolution, and for Figure 2, please specify the Gender categories. Table 2 would suggest remove the Ref group and put it in the footnote. Also please check on grammar and sentence structures, as some sentences are abit confusing.

Reviewer #2: The manuscript addresses an interesting topic. The data are original and the methods sound for the data at hand. The results are well described and support the conclusions. Some comments follow.

1. I really enjoy reading this work. The employed statistical methods are sound and advanced enough to model the main data features. I have just some minore notes:

a) I see that Gaussian random effects are often taken for granted, but please comment on how tenable this assumption is. Non-parametric or discrete or skew or heavy-tailed random effects can be considered instead. Of course, you use an R package, and this may be difficult to address, but some discussion is required at least.

b) Please, provide more details on the computational details, e.g. the burn-in, the priors, etc., and show the convergence of the Markov chains in a supplementary.

c) Random slopes are considered, this is fine with me. I am wondering if the model can be extended to allow for correlated random effects between the longitudinal and the survival processes. As it stands, a shared random effect approach is considered. Some examples are available in the statistical literature, see e.g. papers published in Statistics in Medicine or Biometrical Journal.

d) The random effects are time-constant. This is a limitation of the modelling. Nowadays, time-varying random effects are commonly used in longitudinal data analysis, and also in the joint modelling with survival processes. I am wondering why you did not allow the random effects to vary over time, e.g. following a Markov chain or an Autoregressive process. A discussion on this point is also required.

2. No matter which approach is considered, the assumptions of which the methods are based must be checked carefully. This aspect is overlooked. A residual analysis should be provided.

3. Collinearity may be an issue, as well as endogeneity. How do you deal with these potential problems affecting the results?

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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 #1: No

Reviewer #2: No

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JOINT MODELING OF LONGITUDINAL CHANGE IN PULSE RATE AND SURVIVAL TIME OF HEART FAILURE PATIENTS TREATED AT ARBAMINCH GENERAL HOSPITAL, SOUTHERN ETHIOPIA

PONE-D-22-24580R1

Dear Dr. Anjullo,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Jaimin R. Trivedi, MBBS, MPH

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 #1: All comments have been addressed

Reviewer #2: 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 #1: Yes

Reviewer #2: (No Response)

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

Reviewer #1: Yes

Reviewer #2: (No Response)

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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 #1: Yes

Reviewer #2: (No Response)

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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 #1: Yes

Reviewer #2: (No Response)

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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 #1: (No Response)

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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 #1: No

Reviewer #2: No

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