Dear Dr MacRae,

Thank you for submitting your manuscript entitled "Measuring multimorbidity: impact of varying the number and selection of conditions on estimated multimorbidity prevalence in a large primary care population dataset" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff as well as by an academic editor with relevant expertise and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Please re-submit your manuscript within two working days, i.e. by Oct 18 2022 11:59PM.

Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine

Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Philippa Dodd, MBBS MRCP PhD

Senior Editor

PLOS Medicine

Dear Dr. MacRae,

Thank you very much for submitting your manuscript "Measuring multimorbidity: impact of varying the number and selection of conditions on estimated multimorbidity prevalence in a large primary care population dataset" (PMEDICINE-D-22-03375R1) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the 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. 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 us at PLOSMedicine@plos.org.

We expect to receive your revised manuscript by Jan 04 2023 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

Please use the following link to submit the revised manuscript:

https://www.editorialmanager.com/pmedicine/

Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

We look forward to receiving your revised manuscript.

Sincerely,

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

plosmedicine.org

-----------------------------------------------------------

Requests from the editors:

GENERAL

Please respond to all editor and reviewer requests detailed below, in full.

Please number the lines in the manuscript starting at 1 at “Abstract” and in continuous sequence thereafter.

We agree with the reviewers (please see below) that the study’s primary goal should be better emphasized/identified and its implications. Further details and clarifications are required throughout, which we agree with. Please revise accordingly.

** We agree that the novelty is a bit lost among the formal data reporting. Please revise in mind of the potential impact of the study outcomes at the patient/policy level **

COMMENTS FROM THE ACADEMIC EDITOR

I reviewed the article and the reviews and I agree with the decision for major revision

ABSTRACT

Please structure your abstract using the PLOS Medicine headings (Background, Methods and Findings, Conclusions).

Please combine the Methods and Findings sections into one section, “Methods and findings”.

Abstract Methods and Findings:

Please ensure that all numbers presented in the abstract are present and identical to numbers presented in the main manuscript text.

Please provide further details on the population (and setting) that the study investigates

Please provide further details as to how conditions were “selected” when considering multimorbidity prevalence (diagnostic coded registers?)

Please clearly define the main outcome measures.

Please quantify the main results with p-values as well as 95% CIs, if not for the purpose of transparent data reporting please provide the reasons why

Please include any important dependent variables that are adjusted for in the analyses.

Please include a summary of adverse events if these were assessed in the study.

In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology.

Abstract Conclusions:

Please replace the sub-heading “interpretation” with “conclusions”

Please address the study implications without overreaching what can be concluded from the data; the phrase "In this study, we observed ..." may be useful.

Please interpret the study based on the results presented in the abstract, emphasizing what is new and what the wider impact of the study outcomes are, without overstating your conclusions.

Please avoid vague statements such as "these results have major implications for policy/clinical care". Mention only specific implications substantiated by the results.

Please avoid assertions of primacy ("We report for the first time....")

AUTHOR SUMMARY

At this stage, we ask that you include a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary

INTRODUCTION

Please see reviewer comments – we agree that limitations to the age of the data-set should be discussed, please do so later in the discussion

METHODS and RESULTS

Page 4, data sources: please define SEP at first use in this section

Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis-- including those made in response to peer review comments-- should be identified as such in the Methods section of the paper, with rationale.

For all observational studies, we ask authors to indicate the following clearly in the manuscript text:

(1) the specific hypotheses you intended to test,

(2) the analytical methods by which you planned to test them,

(3) the analyses you actually performed, and

(4) when reported analyses differ from those that were planned, transparent explanations for differences that affect the reliability of the study's results. If a reported analysis was performed based on an interesting but unanticipated pattern in the data, please be clear that the analysis was data-driven.

Please quantify the main results with p-values as well as 95% CIs, if not for the purpose of transparent data reporting please provide the reasons why

When a p value is given, please specify the statistical test used to determine it.

Please remove role of the funding source from the end of the methods section and include only in the manuscript submission form.

TABLES and FIGURES

We agree the reviewer that the figures rather undersell the data. The titles are rather inaccessible and difficult to understand and don’t explain the figure contents clearly for the reader. Please revise throughout, including the supporting files.

To make figures more accessible to those with colorblindness please consider avoiding the use of red/green

Please ensure that each figure/table (including those in supporting files) has an appropriate caption

Please define all abbreviations (for example: IMD, RR) in the figure/table captions

Please indicate whether analyses are adjusted and if so, please state the caption inwhich factors are adjusted for and report unadjusted analyses for comparison

DISCUSSION

Please present and organize the Discussion as follows: a short, clear summary of the article's findings; what the study adds to existing research and where and why the results may differ from previous research; strengths and limitations of the study; implications and next steps for research, clinical practice, and/or public policy; one-paragraph conclusion. Please remove the sub-heading conclusion.

Please expand your discussion to better focus on the study aim and implication of the outcomes, without overstating – see also reviewer 2 comments

Please remove all “declaration” statements from the end of the discussion and include only in the submission form. The section “Author contributions” may remain under its own heading.

REFERENCES

Please use the "Vancouver" style for reference formatting, and see our website for other reference guidelines here: https://journals.plos.org/plosmedicine/s/submission-guidelines#loc-references

For in-text reference call outs citations should be placed in square brackets and preceding punctuation like so [1,2,3,4] or [1-4,6]. Please amend throughout.

In the bibliography please list up to but no more than 6 author names followed by et al (where more than 6 authors contribute to the study).

Journal name abbreviations should be those found in the National Center for Biotechnology Information (NCBI) databases.

Comments from the reviewers:

Reviewer #1: Statistical review

This paper uses data from a large set of patients in England to investigate how different definitions of multimorbidity affect prevalence estimates. The authors also present this stratified by socioeconomic level, sex and age.

Generally the paper presents an important message for multimorbidity research. The statistical methods used are straightforward, as just prevalence estimates and confidence intervals are needed. I had very few comments, which are presented below:

1. Statistical methods: "To examine the effect of the number of conditions considered in the count, multimorbidity prevalence was calculated when considering the most common two conditions, followed by the most common three conditions, the most common four conditions, etc, for every number up to considering all 80 conditions in the count (Information Panel). To do this, conditions were ordered from most to least prevalent (Supplementary Table 1) and added in turn to each new count" Although this procedure would give the highest multimorbidity prevalence in the case that conditions are independent from one another, it's possible it might not do so if common conditions are correlated. E.g. if considering conditions 1, 2 and 3 in descending prevalence, the prevalence of '1 and 2' might be less than '1 and 3' if conditions 1 and 2 co-occur in a lot of patients. This is just a picky point really and I don't think it makes sense to change what the authors did in any way!

2. Statistical methods: can some more intuition be provided about the direct standardisation to the age structure of the population?

3. Page 8: "29.5% (95%CI 29.5-29.9%)" - is this correct? The lower boundary and the point estimate are the same.

4. Discussion: are the prevalence estimates generally an underestimate due to potential under-diagnosis of some conditions?

James Wason

Reviewer #2: Thank you for the opportunity to review this work. In their manuscript, the authors explore how various definitions of multimorbidity influence its estimated prevalence. As the authors acknowledge, the growing attention to multimorbidity - and its highly varied operationalization - has contributed to methodological variation and biases in the literature. Overall, this manuscript covers an important aspect of multimorbidity research.

I have a few comments for the authors to consider. Overall, though, I think the paper would benefit from identifying the primary goal and really tightening up the methods, results, and discussion around this. It was, at times, a bit hard to follow. I am not advocating for removing any of the current analyses, but rather making sure they are presented in a way that easily conveys the overarching theme and story while highlighting the important and novel aspects of this work.

Major:

1. Introduction: the authors state "it is common for authors not to explain the procedure used to decide which conditions they consider in the count" - I don't think this is necessarily true. Instead, there's often a 'recycling' of previously published lists. This could be reframed to highlight that the heterogeneity the authors are exploring is not due to authors not presenting information.

2. The authors acknowledge in the introduction that the relationship between multimorbidity and time is important to note given its growing prevalence. However, the data the authors analyze is now nearly 7 years old. While I doubt it would make any meaningful change in the results, the authors should consider acknowledging the datedness of these data and whether they believe this influences their findings at all.

3. Would the authors consider making Supplemental Table 1 part of the main text? I think the list of included conditions is the crux of this study. I know it's visually unappealing, but I think could be important.

4. Could the authors, in the methods, more clearly state that they included every condition mention in any of those studies? It seems to me that is what the authors did, but I think this needs to be made explicitly clear.

5. The approach to use a relative risk and evaluate the appropriate 'cutoff' given those 80 conditions is an interesting approach but could be better setup in the introduction and the methods. It's a bit confusing, right now, the various comparisons that are being made. Indeed, I'd encourage the authors to consider an approach where they explicitly and succinctly lay out all their analyses. For example, "We conducted a suite of comparisons including: ____."

6. The relative risk analysis seems to be the most novel part of this studied but is not as prominently featured. I would encourage the authors to restructure their manuscript focusing on this if they also believe it's the most novel. Right now, some of the most interesting findings feel a bit buried in the analysis.

a. Similarly, it's unclear what the intermediary analyses contribute. For example, "When considering only the two conditions…" as presented in the results. While I understand this was a step along the way, I'm not sure that any study would ever pick only two conditions to estimate the prevalence of multimorbidity.

b. Additionally, I think the first sentence of the discussion doesn't highlight the most important findings. Of course, when it's 2 versus 80 there is a large difference. There are several other findings that are better to highlight - for example the sentence beginning "Second, multimorbidity…"

Minor:

1. The authors could remove the date from the abstract methods.

2. The abstract findings are hard to follow without the additional context presented in the full manuscript. I would encourage the authors to try to restructure their findings to make it more interpretable.

3. Could the authors instead spell out "November 30, 2015" since DD/MM/YY is not standard globally.

4. Please mention the funders in the methods.

5. Please define "IMD" in Table 1.

Reviewer #3: Dear editor,

Thank you for allowing me to read such an interesting manuscript.

I believe that the manuscript was well written and that the research was presented in a way that was easy to follow and understand. I think the statistics were adequately explained and their meaning was easy to understand.

I have only one question for the authors: what were the criteria for choosing some condition lists like the ones from Diederichs, Fortin, Ho, Barnett, Salive, but not others that are well know such as O'Halloran and N'Goran (particularly in primary care settings)?

- O'Halloran J, Miller GC, Britt H. Defining chronic conditions for primary care with ICPC-2. Fam Pract. 2004 Aug;21(4):381-6. doi: 10.1093/fampra/cmh407. PMID: 15249526.

- N'Goran AA, Blaser J, Deruaz-Luyet A, Senn N, Frey P, Haller DM, Tandjung R, Zeller A, Burnand B, Herzig L. From chronic conditions to relevance in multimorbidity: a four-step study in family medicine. Fam Pract. 2016 Aug;33(4):439-44. doi: 10.1093/fampra/cmw030. Epub 2016 May 6. PMID: 27154549.

Best regards.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. MacRae,

Thank you very much for re-submitting your manuscript "Measuring multimorbidity: impact of varying the number and selection of conditions on estimated multimorbidity prevalence in a large primary care population dataset" (PMEDICINE-D-22-03375R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by 3 reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

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.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Feb 15 2023 11:59PM.   

Sincerely,

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Requests from Editors:

GENERAL

Thank you for your detailed and considerate responses to previous editor and reviewer requests. Please see below for further minor revisions.

DATA AVAILABILITY STATEMENT

Thank you for making your data available.

A point for clarification - in one section of the manuscript submission form you state that some restrictions will apply to your data availability but subsequently you go on to state that all relevant data are included in the manuscript and supporting files. I have detailed our data availability statement below for your information, please clarify/revise/expand your statement as necessary.

PLOS Medicine requires that the de-identified data underlying the specific results in a published article be made available, without restrictions on access, in a public repository or as Supporting Information at the time of article publication, provided it is legal and ethical to do so. Please see the policy at

http://journals.plos.org/plosmedicine/s/data-availability

and FAQs at

http://journals.plos.org/plosmedicine/s/data-availability#loc-faqs-for-data-policy

PLOS defines the “minimal data set” to consist of the data set used to reach the conclusions drawn in the manuscript with related metadata and methods, and any additional data required to replicate the reported study findings in their entirety. Authors do not need to submit their entire data set, or the raw data collected during an investigation. Please submit the following data:

The values behind the means, standard deviations and other measures reported;

The values used to build graphs;

The points extracted from images for analysis.

For each data source used in your study:

a) If the data are freely or publicly available, note this and state the location of the data: within the paper, in Supporting Information files, or in a public repository (include the DOI or accession number).

b) If the data are owned by a third party but freely available upon request, please note this and state the owner of the data set and contact information for data requests (web or email address). Note that a study author cannot be the contact person for the data.

c) If the data are not freely available, please describe briefly the ethical, legal, or contractual restriction that prevents you from sharing it. Please also include an appropriate contact (web or email address) for inquiries (again, this cannot be a study author).

TITLE

Suggest the following to align better with PLOS Medicine’s preferred style,

The impact of varying the number and selection of conditions on estimated multimorbidity prevalence: a cross sectional study using a large, primary-care population dataset

STATISITICAL REPORTING

Thank you for including p values. Please ensure that throughout the manuscript including in the tables, figures and supplementary files p is reported as p <0.001 (not .001 or .0001) and where higher as p=0.002 (not .002), for example.

Throughout, suggest reporting statistical information as follows: X% (95%CI [X,Y] p <0.001)

- Note the use of square parentheses around upper and lower confidence limits

- Note the use of a comma instead of a hyphen (as these can be confused with negative values) to separate upper

and lower limits

- Note the reporting of p values as detailed above

ABSTRACT

Line 30: suggest “We conducted….” Or something similar

Line 32: sentence beginning “Outcome…” is rather long and could be more accessible, please revise

Line 35: please ensure that HDR[-UK] is defined for the reader

Lines 38 - 46: the word is “prevalence is mentioned a number of times, might it be helpful to remind the reader that you are reporting multimorbidity prevalence at some point, we leave it to your discretion bt it may be worth considering.

Line 42: is the word “prevalence” required twice here or is this a typo? Please clarify/revise

Line 54 - 55: we suggest avoiding naming the lists here as the reader is yet to learn what all the lists are. See comments below also. Suggest, “These findings imply that there is a need for a standardised approach to defining multimorbidity.” Then go on to state (concisely) how your study helps to solve this problem.

AUTHOR SUMMARY

Line 64: “in half of studies…” suggest make into a separate bullet point

Line 67: suggest “2” instead of “two to 285 (median 17).”

Line 68: perhaps one line stating why? i.e. comparability of study outcomes, generalisability etc

Line 72: suggest “and the impact on multimorbidity prevalence” perhaps?

Line 73: It would be helpful for the reader to elaborate here – what were the differences, briefly

Line 75: this won’t mean anything to the reader as it hasn’t been introduced anywhere in the text apart the abstract but without adequate context (see above for a similar point) suggest either removing/modifying this statement or revising the summary (and abstract) accordingly such that it’s clear to the reader what this is/means. For example, you could expand bullet point 1 of this sub-section to include (some examples) of the lists you used to derive counts and then go on to state which of these were most reliable, as we understand things.

Line 83: suggest removing this statement as it is best placed as part of a discussion

** The early part of your introduction, description of study design in your methods section and, the early part of your discussion summarise things very well and may be helpful with the revisions to your author summary **

REFERENCES

Please ensure that punctuation follows, not precedes, in-text reference call-outs. For example, line 94, “…systems worldwide.[1]” should read, “…systems worldwide [1]. Please check and amend throughout

SOCIAL MEDIA

To help us extend the reach of your research, please provide any Twitter handle(s) that would be appropriate to tag, including your own, your coauthors’, your institution, funder, or lab. Please detail any handles you wish to be included when we tweet this paper, in the manuscript submission form when you re-submit the manuscript.

Comments from Reviewers:

Reviewer #1: Thank you to the authors for addressing my previous comments well. I have no further issues to raise.

Reviewer #2: The authors have thoughtfully addressed the points raised. Thank you.

Reviewer #3: The authors have responded to the remaining comments made by me.

Thank you and best wishes.

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr. MacRae,

Thank you very much for re-submitting your manuscript "The impact of varying the number and selection of conditions on estimated multimorbidity prevalence: a cross-sectional study using a large, primary care population dataset" (PMEDICINE-D-22-03375R3) for review by PLOS Medicine.

I have discussed the paper with my colleagues and I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

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.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.  

We look forward to receiving the revised manuscript by Feb 23 2023 11:59PM.   

Sincerely,

Philippa Dodd, MBBS MRCP PhD

PLOS Medicine

plosmedicine.org

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Requests from Editors:

GENERAL

Thank you for your responses to previous editor requests.

Your author summary needs further revision before we can publish your manuscript. Please see below

AUTHOR SUMMARY

* What did the researchers do and find – this section should be no more than 4 bullet points.

Without reading other parts of the manuscript, it’s difficult to understand what you did. Further some points, to me seem to be illogically ordered. Please see specific points below and revise accordingly.

Line 74 and line 78: suggest combining (and shortening) these points into one point with additional details about what the “lists” are, for example, “We examined nine published condition lists used to define and measure co-morbidity, multi-morbidity and its prevalence. We combined different numbers and types of conditions (detailed in these lists?) to determine how multimorbidity prevalence changed with varying classifications/definitions… All conditions were counted in the same way….” or something similar

The statement currently at line 76 should then follow the above

Line 84: should precede that at line 81

** What do these findings mean – this section should explain the implications of your study findings only.

Line 90: The first point here justifies your methodology and seems inappropriately placed. The sentence is also rather long. Please remove this. If you think this point is important to make, then it should be made in the “what did the researchers do and find” section (see above).

Line 96: When reading the full summary, it suggests that using lists which report “highest” multimorbidity prevalence is advisable. Please (concisely) elaborate as to why this is the case – do these yield more consistent results (?), for example

Any attachments provided with reviews can be seen via the following link:

[LINK]

Dear Dr MacRae, 

On behalf of my colleagues and the Academic Editor, Professor Aaron Kesselheim, I am pleased to inform you that we have agreed to publish your manuscript "The impact of varying the number and selection of conditions on estimated multimorbidity prevalence: a cross-sectional study using a large, primary care population dataset" (PMEDICINE-D-22-03375R4) in PLOS Medicine.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. 

PRESS

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We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine, it has been a pleasure handling your manuscript. We look forward to publishing your paper. 

Best wishes,

Pippa 

Philippa Dodd, MBBS MRCP PhD 

PLOS Medicine