PONE-D-23-16416A STUDY PROTOCOL FOR PREDICTORS OF POST-DISCHARGE MORTALITY AMONG CHILDREN AGED 5-14 YEARS ADMITTED TO TERTIARY HOSPITALS IN TANZANIA: A PROSPECTIVE OBSERVATIONAL COHORT STUDY.PLOS ONE

Dear Dr. MELEKI,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 02 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Deogratias Munube

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript. 

Additional Editor Comments:

Dear Author,

Thank you for the submission. I have provided a few comments to improve your manuscript. Starting with the abstract. this is inconsistent with the whole body of the study protocol. The protocol needs a review of the English grammar. The methods described needs to be improved. For example, the method of recruitment is inconsistent. In one sentence, it is reported that the participants will be conveniently recruited and in another sentence consecutively recruited. The other need to be consistent. The justification for the study does include lack of studies in sub Saharan Africa. However, there are several studies referenced in East Africa. The authors need to improve the justification for the study. The list of abbreviations needs to be listed in alphabetical order. The author indicates that he did not receive any funds but later states that his hospital provided funds. This needs to be corrected. The author acknowledges the contribution of the local university for providing HINARI, this needs to be clarified. Did the university buy the HINARI account for the author. The author does indicate that this is his masters thesis project and does not describe if this is a requirement for his university to publish the protocol? The outcomes stated in the protocol is not consistent. The author needs to correct the impression that the initial primary outcome varies in the manuscript. The study sites need to be clearly described such that a reader understands why the three hospital sites need to be used. The process of recruitment and follow up needs to be clearly described. The telephone call script needs to be added to the protocol. The verbal autopsy guides needs to be included in the manuscript. For the confirmation of the possible cause of death at home or in the community, an document needs to be added to show the reader what process will be used to get that information from the parent or care giver. In the submission, it is indicated that there are no data tables submitted but in the manuscript there are two tables referenced. Are these dummy tables?

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

**********

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

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study protocol provides a clear description of the research design and objectives. The authors aim to investigate post-discharge mortality among children aged 5-14 years in Tanzania and identify predictors of mortality at 3 months after discharge. The protocol outlines the study setting, sample size calculation, inclusion and exclusion criteria, variables to be collected, data collection methods, data management procedures, and data analysis plan.

The strengths of the study protocol include its prospective observational cohort design, which allows for the examination of multiple predictors on post-discharge mortality. The inclusion of three different tertiary hospitals increases the generalizability of the findings. The enrollment of consecutive participants and the involvement of research assistants who are not directly involved in patient care help minimize bias. The use of structured questionnaires and a modified verbal autopsy tool enhances data collection.

However, there are a few areas where the protocol could be improved.

1. The protocol lacks a clear research question or hypothesis, which would provide a focused direction for the study. Though some clues about what the study seeks to achieve can be found in the concluding part of the background, no hypothesis has been proposed to direct the focus of the study.

2. While the candidate variables for predicting post-discharge mortality are listed, there is no explicit explanation of their rationale or theoretical basis. Providing this information would strengthen the study's justification for selecting these variables.

3. The authors have not provided details about the data collection approach. The protocol could benefit from a more detailed description of the data collection process, including how the structured questionnaires will be administered and the training provided to the research assistants. It would also be helpful to clarify how missing data will be handled and accounted for in the analysis.

4. In the data analysis section, the protocol states that univariable and multivariable Cox regression analyses will be used to determine factors associated with mortality. However, there is no mention of potential confounding variables or how they will be addressed in the analysis. It would be important to consider potential confounders and adjust for them in the multivariable analysis to obtain more accurate estimates of the predictors' effects. A protocol must necessarily show more details about the study, accounting for possible limitations are hoe the

5. The discussion section provides a brief overview of the study's aims and potential implications, This section could be expanded to include a more thorough interpretation of the results to expect. The limitations section highlights some potential limitations, such as missing data and the challenges of conducting verbal autopsies over the phone. However, it would be beneficial to discuss these limitations in more detail and address strategies to mitigate them.

Overall, the study protocol in its current form does not meet the requirements of a study protocol. It is not detailed and elaborate enough to allow for replication of the study. By addressing the aforementioned areas of improvement, the protocol can be further strengthened to ensure the study's rigor and validity.

**********

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

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

A STUDY PROTOCOL FOR PREDICTORS OF POST-DISCHARGE MORTALITY AMONG CHILDREN AGED 5-14 YEARS ADMITTED TO TERTIARY HOSPITALS IN TANZANIA: A PROSPECTIVE OBSERVATIONAL COHORT STUDY.

PONE-D-23-16416R1

Dear Dr. ELTON Roman Meleki

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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,

Deogratias Munube

Academic Editor

PLOS ONE