PONE-D-24-47106Randomised controlled trials for improving health outcomes for people living with multiple long-term conditions: protocol for a systematic review of methodological approaches, risk of bias and reporting qualityPLOS ONE

Dear Dr. Gray,

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 Feb 09 2025 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,

Paolo Landa, Ph.D.

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. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript. 

3. Thank you for stating the following in the Competing Interests section: 

“KK is National NIHR Applied Research Collaborations theme lead for Multiple Long Term Conditions and is Co-Chair of the NIHR Cross NIHR Collaboration for Multiple Long Term Conditions.

SAS is President of the UK Society of Behavioural Medicine. She has also been a member of the NIHR HTA Clinical Evaluations and Trials Committee (2016-2020), the Commissioning Panel for the NIHR Policy Research Programme (2019-2022); the Chief Scientist Office Health Improvement Protection and Services committee (2018-2023).

RST and SAS are currently co-chief investigators on an NIHR funded PERFORM programme (NIHR202020), developing and evaluating the impact of a exercise-rehabilitation intervention for people with multiple long-term conditions. 

LJG, KK and ND are Co-Is: Davies M (PI) Type 2 Diabetes (T2D) in 18 – 40-year-olds: A Multifactorial Management Intervention to Address Multimorbidity in Early-Onset T2D in Adults (The M3 Research Programme). NIHR Programme Grants for Applied Research. £2,570,619.00. Start date Aug 2021 (5 years).”

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to  PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. 

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

4. We notice that your supplementary materials are included in the manuscript file. Please remove them and upload them with the file type 'Supporting Information'. Please ensure that each Supporting Information file has a legend listed in the manuscript after the references list.

Additional Editor Comments:

Many updates are required for improvement. Please follow the indications of the reviewer

[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: Partly

**********

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: Yes

**********

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: 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

**********

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: Thank you for the opportunity to review this paper. I think this paper is worth publishing following some updates, especially a major revision of the methods section.

**********

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.

Attachments

Attachment

Submitted filename: PLOSONE_Multimorbidity_SRprotocol_20241202.docx

PONE-D-24-47106R1Randomised controlled trials for improving health outcomes for people living with multiple long-term conditions: protocol for a systematic review of methodological approaches, risk of bias and reporting qualityPLOS ONE

Dear Dr. Gray,

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 May 09 2025 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,

Paolo Landa, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

Please consider all the information provided by the reviewers in the revision process

[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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

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 #2: No

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: Yes

**********

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 #2: No

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: 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 #2: Thank you for pursuing research into this important topic.

Given your interest in trials specifically, I would assume you are searching Cochrane Central rather than the entire Cochrane Library - please clarify the abstract. I also find it odd to identify the interface in the abstract for only one of the databases; would suggest deferring that detail to the text.

In defining the topic, you use the terminology "long duration" - what does this mean specifically? How long?

Is the "two-thirds of adults aged over 65 will be affected" estimate specific to England, as in the preceding clause, or globally? Suggest clarifying.

"Despite more people living with MLTCs than single conditions" - what is the source for this claim? I'm not seeing it in the following reference.

The manuscript would benefit from a thorough copy-editing for clarity and flow.

The body of the manuscript should identify specifically the interfaces through which each database is being searched, and see comment above about Cochrane Library.

"The start date of January 1999 was chosen, as this is when the first trial in MLTCs was reported in a previous systematic review". The review referenced was limited to those taking place in primary care and community settings, which does not appear to be the case for your review - there may well be earlier trials in other contexts.

A rationale should be provided for limiting results to English.

Was consideration given to searching the grey literature? Its absence should be noted as a limitation.

What is the rationale for excluding secondary/subgroup analyses?

The Scopus search strategy appears to be missing parentheses around the multimorbidity concept. Also why not use the same proximity search strings as for the other databases?

The Medline search string presented appears to be missing several lines - the final line attempts to limit line 21, but the strategy before that point only has 17 lines.

It appears that some literature uses the alternative term "polymorbidity" - this should be included in the search.

Reviewer #3: Dear Authors,

It was interesting reading your revised protocol. The addressed topic is fundamental to improve the quality of life of people living with multiple long-term conditions. Your revised manuscript addressed almost all the previous reviewer comments which align completely with my feedback. A few points need to be re-addressed as follows:

1. It is acceptable to limit the inclusion of studies to English. However, it would be recommended to justify this language restriction as long as you are not searching for studies conducted only in the UK.

2. You did not separate the risk of bias into a different subsection, which is recommended for better structure and readability.

3. Lastly, it is recommended to fill out the PRISMA-P checklist and add it as a supplementary file.

Otherwise, your protocol is to be accepted and look forward toward reading your final results.

Reviewer #4: The analysis of methodological aspects of RCTs on multimorbidity is a valuable research aim. However, the language and structure of this protocol require significant improvements.

Major Issue = Inclusion/Exclusion Criteria

1) INDEX condition

The sentence: "In line with the reviews by Smith et al, trials with an index condition ... will be excluded." needs further clarification.

Specifically, if a trial includes patients with diabetes (DM) and hypertension (HTN), how will it be classified?

Does inclusion depend on how the study defines the patient population? For example:

If a study states, “we evaluated diabetic patients with hypertension,” does this make diabetes the index condition, leading to exclusion?

If it states, “we evaluated hypertensive patients with diabetes,” does this make hypertension the index condition, leading to exclusion?

If it simply states “we evaluated patients with diabetes and hypertension,” does this qualify as a multimorbidity study?!

or you would exclude studies on any specific combination of disorders and only include those RCT with multimorbidity? this part of selection is not clear.

These criteria must be explicitly defined so that others can replicate the systematic review and consistently determine which trials are included.

Minor issues:

1) Search Start Date (January 1999)

The authors justify using January 1999 as the starting point, stating that “this is when the first trial in MLTCs was reported in a previous systematic review.” However, the following reference suggests relevant trials exist before 1999: https://doi.org/10.7326/0003-4819-126-12-199706150-00004.

Given this, it may be more appropriate not to limit the search by a starting year unless a strong rationale is provided.

2) Grammatical and Stylistic Issues

The manuscript contains several grammatical errors. For instance, in the first two sentences of the introduction, the authors inconsistently use “is” and “are” when referring to MLTCs.

Careful proofreading is required to ensure grammatical consistency and readability.

3) Unprofessional Referencing

If the first sentence is a direct quotation, the source must be explicitly stated.

Additionally, citing four references for a simple statement is excessive and unprofessional. The authors should ensure that only the most relevant sources are cited.

Reviewer #5: The edited manuscript has been checked over as well as the comments and responses. Seems fine after responding to all the requested comments from the reviewers.

**********

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 #2: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: 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.

PONE-D-24-47106R2Randomised controlled trials for improving health outcomes for people living with multiple long-term conditions: protocol for a systematic review of methodological approaches, risk of bias and reporting qualityPLOS ONE

Dear Dr. Gray,

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.

==============================

ACADEMIC EDITOR: the reviewers proposed a set of changes required in order to improve the manuscript. These modifications are essential in order to advance with the revision process. Please follow the indications provided by the reviewers.

==============================

Please submit your revised manuscript by Jun 08 2025 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,

Paolo Landa, Ph.D.

Academic Editor

PLOS ONE

[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 #4: Yes

Reviewer #6: Partly

Reviewer #7: Yes

Reviewer #8: 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 #4: Yes

Reviewer #6: Yes

Reviewer #7: Yes

Reviewer #8: Yes

**********

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 #4: Yes

Reviewer #6: Yes

Reviewer #7: Yes

Reviewer #8: Yes

**********

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 #4: Yes

Reviewer #6: Yes

Reviewer #7: Yes

Reviewer #8: 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 #4: Yes

Reviewer #6: No

Reviewer #7: Yes

Reviewer #8: 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 #4: Thank you for making these revisions. The quality of the manuscript has improved significantly. I have no further comments.

Reviewer #6: The manuscript improved greatly after the authors followed most of the reviewers comments.

I would like authors to reconsider some points regarding the reference section. some references have a link to download a file but when we click on it, it leads to empty web page.

Therefore, if the reference is a website, please input the link of the website instead of a link to a file download. also mention the date you access it to retrieve the information. (accessed on xx day xx month 202x year)

this reference also need to be rewritten:

International research community in multimorbidity. Multimorbidity publications 2021 [Available from: https://crmcspl-blog.recherche.usherbrooke.ca/.

This is a blog which has its own criteria for referencing:

Author of blog post. Year that the post was published or last updated. Title of blog post. Day/month of published or updated blog post. Available at: URL. (Accessed: date)

Do you mean all articles in this website page are this single reference?

Reviewer #7: Thank you for a sophisticated protocol for a systematic review. I have a few questions about your protocol.

"Not doing a meta-analysis due to the research question" needs some more clarification. You are including RCT studies and your PICO is in quantitative format. This means the results should be able to be running a meta-analysis. The reason does not appear to be valid.

Reviewer #8: I retaliate what the second and fourth reviewers said, that a thorough grammatical check should be carried out before submitting the manuscript. (Check out line 197 and 198 and rectify them to make grammatical sense).

Otherwise thank you for choosing to concentrate on this unique research area.

**********

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 #4: No

Reviewer #6: Yes:  Doaa Husham Majeed Al-saadi

Reviewer #7: Yes:  Thomas Aaron Ricks

Reviewer #8: 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.

Randomised controlled trials for improving health outcomes for people living with multiple long-term conditions: protocol for a systematic review of methodological approaches, risk of bias and reporting quality

PONE-D-24-47106R3

Dear Dr. Gray,

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,

Paolo Landa, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: