-->PONE-D-25-45216-->-->Patterns and predictors of variability in patient-generated daily pain severity collected via a mobile health smartphone app-->-->PLOS One

Dear Dr. Schultz,

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.

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Mohamad K. Abou Chaar, M.D.

Academic Editor

PLOS One

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[This study was supported by the Centre for Epidemiology Versus Arthritis (grant number 21755). Cloudy with a Chance of Pain was funded by Versus Arthritis (grant reference 21225), with additional support from the Centre for Epidemiology (grants 21755 and 20380). TH receives funding from the Royal Society (grant number INF/R2/180067) and the Alan Turing Institute for Data Science and Artificial Intelligence.].

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[This study was supported by the Centre for Epidemiology Versus Arthritis (grant number 21755). Cloudy with a Chance of Pain was funded by Versus Arthritis (grant reference 21225), with additional support from the Centre for Epidemiology (grants 21755 and 20380). Ethical approval for Cloudy with a Chance of Pain was from the University of Manchester Research Ethics Committee (ref: ethics/15522) and the NHS IRAS (ref: 23/NW/0716). TH receives funding from the Royal Society (grant number INF/R2/180067) and the Alan Turing Institute for Data Science and Artificial Intelligence. The funders of the study had no role in study design, data interpretation, writing of the manuscript, or the decision to submit for publication.]

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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

[This study was supported by the Centre for Epidemiology Versus Arthritis (grant number 21755). Cloudy with a Chance of Pain was funded by Versus Arthritis (grant reference 21225), with additional support from the Centre for Epidemiology (grants 21755 and 20380). TH receives funding from the Royal Society (grant number INF/R2/180067) and the Alan Turing Institute for Data Science and Artificial Intelligence.]

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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: I Don't Know

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.-->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

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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

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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: Review of PONE-D-25-45216:

Patterns and predictors of variability in patient-generated daily pain severity collected via a mobile health smartphone app (Schultz et al.)

Overview:

This manuscript addresses an important question: how daily pain variability can be characterized using high-frequency patient-generated data from a large mHealth cohort. The dataset is rich and the basic scientific-clinical question is solid. The work builds on the prior “Cloudy with a Chance of Pain” studies and extends them meaningfully by focusing specifically on variability. That said, this paper has some methodological and mostly reporting flaws that warrant correction before publication.

Major Comments:

1. This paper is extremely technical. As a physician with only moderate understanding of statistics I found it very hard to understand. Moreover, while I have faith in the authors that it is is mathematically correct (too technical for me to review), I could not make out the narrative of the paper, i.e, there is simple “big picture” section guiding the reader through the logic of the analysis before the numbers appear. Key technical terms (AC, PAC, MSSD) are not well explained for the non-expert readers. Understanding these is key to understanding the paper entirely.

2. Similarly, I feel like the paper focuses too much on mathematical findings and too little on patient-centered outcomes. It jumps between terms like stable weeks, variability metrics, LASSO-selected predictors and without interperting these into outcomes that matter to patients. This also menifests in the fact the discussion is very short compared to other parts of the manuscript.

3. The Methods section is in my view overly long and somewhat cumbersome. Honestly, although reading it twice, I am not sure I understood the Methods correctly. It includes many internal definitions (e.g. available weeks, covariate score), the reasoning behing choosing different options in the methods (e.g. why a week starts on Monday), very in-depth statistical data, and goes into so much detail about the methodology that for the reader unfamiliar with the previous work, it becomes impossible to understand. I recommend revising the Methods to make it much shorter – e.g. one parageaph for each of the subsections. I also recommend adding an explanatory figure. If the authors still want to include what’s currently described in the Methods, I recommend adding a supplementary appendix.

4. All tables and figures require legends (which include explanation of acronyms), and should be referenced from and support the arguments made in the main text. Currently many just report a lot of data. Similarly I feel that some data reported in the supplement (e.g. demographics) should be transferred to the main manuscript file, and vice versa.

5. This study includes several limitations that should either be mitigated, better reported, or at the very least mentioned in the Discussion (which oddly does not include a “limitations” section). These include:

A. substantial loss of weeks due to incomplete covariate data

B. Demographics are highly skewed toward females and toward younger patients.

C. It is unclear whether complete weeks differ systematically in key outcomes (pain levels, variability) compared to incomplete weeks.

6. Conclusions section is very long and includes parts that don’t belong in it. Conclusions should be one paragraph summarizing the paper, everything else belongs in the general Discussion.

Minor Comments:

1. Abstract mentions four clusters but does not explain clustering methodology. Suggest including a short explanation as exists in the full paper (e.g. no, mild, moderate and severe pain). In general, for the sake of simplicity I recommend using the actual term (mild-moderate-severe) instead of the A-B-C-D labeling which may add confusion.

2. I find it odd that two figures in the paper describe a hypothetical patient. Figures should depict data collected.

3. References: Schneider et al. (2012) is duplicated.

4. Figure 3b (graphical distribution of pain differences) is informative but difficult to interpret without a color scale or more explicit labeling.

5. Note some minor typos throughout the manuscript (e.g. inteference).

Reviewer #2: I congratulate you for your detailed analysis and meticulously prepared research, as well as for your clearly written article. However, there are some points that I would like to draw attention to. -What does "pain interfence" mean, which you mentioned on page 11, lines 358-359? Could you explain this a little more?

- The conclusion section is longer than the discussion section. Shouldn't the information in the conclusion section be included in the discussion section?

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Reviewer #1: No

Reviewer #2: Yes: Ridvan IsikRidvan Isik

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-->PONE-D-25-45216R1-->-->Patterns and predictors of variability in patient-generated daily pain severity collected via a mobile health smartphone app-->-->PLOS One

Dear Dr. Schultz,

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 consider modifying the conclusion. It should be brief and concise, describing only key takeaways from your research. -->-->==============================

Please submit your revised manuscript by Apr 11 2026 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.. 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 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 . 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,

Mohamad K. Abou Chaar

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. 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.

Additional Editor Comments :

Dear Authors,

Thank you for the revision and for addressing all of the comments. I do have one additional comment regarding the conclusion section. To me, the first three paragraphs of the conclusion would fit better in the discussion section. I understand the PLOS ONE format requirements, but at the end of the day, the conclusion should be a brief and focused summary of the main takeaway, its importance, and the key implication of the study rather than an extended discussion. This will add additional overall clarity to your manuscript.

Thank you,

Mohamad K. Abou Chaar, M.D.

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

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: (No Response)

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: Yes

**********

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

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

**********

-->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.-->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

**********

-->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: Yes

**********

-->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: I appreciate the authors' work to revise the paper, it is indeed more readable now and with clearly stated findings.

I still think it is overly technical, that some methods and results belong in a supplementary appendix, and that the conclusions section should be further refined, all as I mentioned in my initial review. I understand the authors disagree with these recommendations, and leave the final decision to the authors and the editor.

Reviewer #2: I appreciate your efforts and the time you spent, as you have adequately addressed all comments and suggestions.

**********

-->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 published, this will include your full peer review and any attached files.

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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 For information about this choice, including consent withdrawal, please see our Privacy Policy .-->.-->

Reviewer #1: No

Reviewer #2: Yes: RIDVAN ISIKRIDVAN ISIK

**********

[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.]

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You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->

Patterns and predictors of variability in patient-generated daily pain severity collected via a mobile health smartphone app

PONE-D-25-45216R2

Dear Dr. Schultz,

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,

Mohamad K. Abou Chaar, M.D.

Academic Editor

PLOS One