PONE-D-23-28616A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitalsPLOS ONE

Dear Dr. Lundstrøm,

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. The protocol describes a study of significance in today's global ageing population. Please consider the reviewers' feedback and queries, particularly addressing the need for more detail on the rationale for the study, to report the protocol according to the SPIRIT guideline, confusion re a pilot study or full randomised trial, and consideration of appropriate analysis tests for your outcome variables.

Please submit your revised manuscript by Dec 28 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Kathleen Finlayson

Academic Editor

PLOS ONE

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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

Reviewer #2: Partly

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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

Reviewer #2: Partly

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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

Reviewer #2: No

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: 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 read and review this protocol manuscript. Overall, I find the protocol relevant and feasible.

I do however, have some suggestions for improvement.

Abstract: overall, I find the language in the abstract inconsistent and in need for revision by a native English speaker.

Especially the Introduction (in the abstract) need a re-writing regarding coherence and language. Consider not to use "often" (also in the manuscript) as it is unspecific tending to appraising.

I find the sentence "There remains limited understanding..." both clumsy and arrogant - what do you know about peoples' understanding? I know, it hasn't been the intention but nevertheless, it is the signal. CIM should be explained (or not used) in the abstract. I struggle a bit to understand the choice of the word "effects" in the aim - are you sure that this is the correct word to use here? or is it rather "impact" or "effectiveness"?

First line in the Methods (in the abstract): should it be: ".. integrated care for patients..."?

Should "patient's" be plural (patients')?

In the last 4-5 lines of the abstract you write in the past tense (were collected, were recorded, assessments involved...) - should this be the present tense or have these actions been carried out?

Introduction

Unless it is due to journal guidelines, please, gather consecutive references in one bracket.

Consider to decrease the use of "often"

The literature used to argue for a recent empirical situation (here: the organisation of healthcare, the number of persons suffering from multi-morbidity and so on) should be recent and not from e.g., 2015, 1996, 2016.

Line 5 regarding the amount of people with complicated multi-morbidity - where is this? still in Denmark?

The coherence between some of the sections in the Introduction is poor - for example the description of the secondary healthcare sector appears a bit out of context.

Reference 15 has not publication year presented in the Reference list.

Line 8 from the bottom of the section: what is a critical potential? please, clarify.

Consider moving the sentences describing that both studies run simultaneously to tie Limitations - it is a bit weird to have this information here.

Aim: this aim corroborates better with the study design and the chosen outcomes - but why does it differ substantially from the aim in the abstract? Please align.

Methods

I wonder why you do not describe that the protocol is guided by the SPIRIT - I would have recommended that but noticed by the end of the manuscript that you have... I do however, then wonder why you haven't followed the guideline? your structure differ completely from the structure recommended by the guideline.

It is stated that the study will take place in the 3rd quarter of2022 - does this mean that the study is completed? before the protocol is published?

Regarding the sample size - why do you think that 30% will dropout? Please, provide a reference for this.

Data

What is meant by "Patient outcome"? should this term be mentioned in the design..?

And why have you chosen to interview 15 patients?

Analyses

In this section, quite new terms are introduced: comparability, health economic evaluation and process evaluation - they should be introduced earlier. Please, align terms in Abstract, Methods, Data and Analyses.

References

The reference list should be scrutinized regarding Danish titles (should be presented in English in square brackets) - for example no4, 5, 25, 42 - and lack of information - for example no 15 without publication year.

Reviewer #2: Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. I look at the manuscript in/with statistical view point, other reviewer(s) look(s) at it with different angle so that in totality the review is very comprehensive. However, there should be efforts from authors side to improve (may be by taking clues from reviewer’s comments). Therefore, please do not limit the revision only (with respect) to comments made here.

COMMENTS: There are a few issues about which I have different opinion and such observations/concerns are given below (since the study is at ‘Protocol’ stage, it is possible to incorporate agreed ones):

In ‘Aim of the pilot study’ section [end of ‘Introduction’, page 5] it is stated that “This paper describes the protocol for a pilot cluster randomised controlled trial to determine the effectiveness of a general practice-based intervention aimed at improving treatment and care for patients with complicated multimorbidity”. Is this a protocol for a pilot cluster randomised controlled trial? I wonder, why (in that case) the word PILOT has not appeared in ‘title’ of the study (then)? In my opinion that is expected. Later in ‘Development of the CIM2 intervention’ section you state that “The study described in this protocol is the execution of phase 3 of the MRC framework for complex interventions”, and accordingly [according to ‘MRC framework’ described by you described in this section] a full-fledged clinical trial is expected. Then why this ‘PILOT’? Actually, the present one seems to be a full-fledged clinical trial.

In ‘Abstract - methods’ section, it is stated that “The primary outcome measure is the patient’s experience of quality of care measured by the Patient Assessment Chronic Illness Care Questionnaire (PACIC). Secondary outcomes include the patient’s health-related quality of life, measured by the EuroQol-5 Domain questionnaire (EQ-5D-5L) and the treatment burden measured by the Multimorbidity Treatment Burden Questionnaire (MTBQ).”. Note that though the measures/tools used are appropriate, all of them are likely to yield data that are in ‘ordinal’ level of measurement [and not in ratio level of measurement {as the score two times higher does not indicate presence of that parameter/phenomenon as double (for example, a Visual Analogue Scales VAS score or say ‘depression’ score)}]. Then application of suitable non-parametric (or distribution free) test(s) is/are indicated/advisable [even if distribution may be ‘Gaussian’ (also called ‘normal’)].

Agreed that there is/are no non-parametric test(s)/technique(s) available to be used as alternative in all situation(s), but should be used whenever/wherever they are available. Therefore, in short use suitable non-parametric test(s)/technique(s) while dealing with data that are in ‘ordinal’ level of measurement even if [despite that] the distribution may be ‘Gaussian’.

In ‘Analyses - Analyses of comparability’ section use of any non-parametric test/technique is/are not proposed. Instead, it is said that “A linear mixed model, will be used for the analysis”. Using mixed-model regression is not wrong at all, but note that this technique [in fact any regression technique(s) for that matter] is/are not originally developed for testing the ‘Group difference(s)’. Head-to-head comparison is expected, as through regression is an indirect/secondary/by-product testing, in my opinion. {Section ‘Analyses of comparability’ mentions that “The secondary analyses will compare scores of the EQ-5D-5L and MTBQ in the intervention group and the control group using the same methods as described.”}

Sample size estimation used is described in ‘Sample size’ section seems to be alright but is little complicated (since not usual). In this (‘Sample size’) section for few assumptions refences are given [example: The difference of interest between the intervention and the control group is Δ=0.36, with a mean value of 2.86, and with an expected standard deviation SD = 1, based on results from earlier studies [33], [34].] but the other important assumption is without any relevant refence(s) [example: The power calculations take a potential Intraclass Correlation Coefficient (ICC) of 0.1 into account.], whereas the sample size estimate depends on all [and so is very much affected due to assumed values without any relevant refence(s)]. Your sample size estimation may be correct, however, raises doubt in mind of most readers. Further, kindly confirm whether the procedure used here, takes care of (i.e., incorporates) ‘30% dropouts assumed’? Otherwise, mind you that 30% (of 175) is 53 and so needed sample size is 228.

The ‘Limitations’ section includes only defining term multimorbidity and this makeing it difficult to compare different multimorbidity studies. Does that mean {according to authors} there are none other(s)? As pointed out in ‘important note’ above “This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ should be assessed separately/independently [one should carefully consider/look at the clinical implications of the study].

In my opinion, to make this article acceptable (which is quite possible), a small amount of re-vision (re-drafting) may be needed. However, please do not limit the revision only (with respect) to comments made here. More improvement is expected. The respected ‘Editor’ may consider accepting/further processing only if found ‘clinical implications’ valuable [i.e., add(s) to clinical knowledge or positively influence clinical practice]. ‘Minor revision’ is recommended.

Important note: This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ [like medical importance, relevance of the study, ‘clinical significance and implication(s)’ of the whole study, etc.] are to be evaluated [should be assessed] separately/independently. Further please note that any ‘statistical review’ is generally done under the assumption that (such) study specific methodological [as well as execution] issues are perfectly taken care of by the investigator(s). This review is not an exception to that and so does not cover clinical aspects {however, seldom comments are made only if those issues are intimately / scientifically related & intermingle with ‘statistical aspects’ of the study}. Agreed that ‘statistical methods’ are used as just tools here, however, they are vital part of methodology [and so should be given due importance]. I look at the manuscript in/with statistical view point, other reviewer(s) look(s) at it with different angle so that in totality the review is very comprehensive. However, there should be efforts from authors side to improve (may be by taking clues from reviewer’s comments). Therefore, please do not limit the revision only (with respect) to comments made here.

COMMENTS: There are a few issues about which I have different opinion and such observations/concerns are given below (since the study is at ‘Protocol’ stage, it is possible to incorporate agreed ones):

In ‘Aim of the pilot study’ section [end of ‘Introduction’, page 5] it is stated that “This paper describes the protocol for a pilot cluster randomised controlled trial to determine the effectiveness of a general practice-based intervention aimed at improving treatment and care for patients with complicated multimorbidity”. Is this a protocol for a pilot cluster randomised controlled trial? I wonder, why (in that case) the word PILOT has not appeared in ‘title’ of the study (then)? In my opinion that is expected. Later in ‘Development of the CIM2 intervention’ section you state that “The study described in this protocol is the execution of phase 3 of the MRC framework for complex interventions”, and accordingly [according to ‘MRC framework’ described by you described in this section] a full-fledged clinical trial is expected. Then why this ‘PILOT’? Actually, the present one seems to be a full-fledged clinical trial.

In ‘Abstract - methods’ section, it is stated that “The primary outcome measure is the patient’s experience of quality of care measured by the Patient Assessment Chronic Illness Care Questionnaire (PACIC). Secondary outcomes include the patient’s health-related quality of life, measured by the EuroQol-5 Domain questionnaire (EQ-5D-5L) and the treatment burden measured by the Multimorbidity Treatment Burden Questionnaire (MTBQ).”. Note that though the measures/tools used are appropriate, all of them are likely to yield data that are in ‘ordinal’ level of measurement [and not in ratio level of measurement {as the score two times higher does not indicate presence of that parameter/phenomenon as double (for example, a Visual Analogue Scales VAS score or say ‘depression’ score)}]. Then application of suitable non-parametric (or distribution free) test(s) is/are indicated/advisable [even if distribution may be ‘Gaussian’ (also called ‘normal’)].

Agreed that there is/are no non-parametric test(s)/technique(s) available to be used as alternative in all situation(s), but should be used whenever/wherever they are available. Therefore, in short use suitable non-parametric test(s)/technique(s) while dealing with data that are in ‘ordinal’ level of measurement even if [despite that] the distribution may be ‘Gaussian’.

In ‘Analyses - Analyses of comparability’ section use of any non-parametric test/technique is/are not proposed. Instead, it is said that “A linear mixed model, will be used for the analysis”. Using mixed-model regression is not wrong at all, but note that this technique [in fact any regression technique(s) for that matter] is/are not originally developed for testing the ‘Group difference(s)’. Head-to-head comparison is expected, as through regression is an indirect/secondary/by-product testing, in my opinion. {Section ‘Analyses of comparability’ mentions that “The secondary analyses will compare scores of the EQ-5D-5L and MTBQ in the intervention group and the control group using the same methods as described.”}

Sample size estimation used is described in ‘Sample size’ section seems to be alright but is little complicated (since not usual). In this (‘Sample size’) section for few assumptions refences are given [example: The difference of interest between the intervention and the control group is Δ=0.36, with a mean value of 2.86, and with an expected standard deviation SD = 1, based on results from earlier studies [33], [34].] but the other important assumption is without any relevant refence(s) [example: The power calculations take a potential Intraclass Correlation Coefficient (ICC) of 0.1 into account.], whereas the sample size estimate depends on all [and so is very much affected due to assumed values without any relevant refence(s)]. Your sample size estimation may be correct, however, raises doubt in mind of most readers. Further, kindly confirm whether the procedure used here, takes care of (i.e., incorporates) ‘30% dropouts assumed’? Otherwise, mind you that 30% (of 175) is 53 and so needed sample size is 228.

The ‘Limitations’ section includes only defining term multimorbidity and this making it difficult to compare different multimorbidity studies. Does that mean {according to authors} there are none other(s)? As pointed out in ‘important note’ above “This review pertains only to ‘statistical aspects’ of the study and so ‘clinical aspects’ should be assessed separately/independently [one should carefully consider/look at the clinical implications of the study].

In my opinion, to make this article acceptable (which is quite possible), a small amount of re-vision (re-drafting) may be needed. However, please do not limit the revision only (with respect) to comments made here. More improvement is expected. The respected ‘Editor’ may consider accepting/further processing only if found ‘clinical implications’ valuable [i.e., add(s) to clinical knowledge or positively influence clinical practice]. ‘Minor revision’ is recommended.

**********

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-23-28616R1A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitalsPLOS ONE

Dear Dr. Lundstrøm,

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.

  In particular, please consider the reviewers' comments below on addressing justification for the study in the introduction and background, and the need for further details of the methods for the interviews and recruitment.

Please submit your revised manuscript by Apr 27 2024 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,

Kathleen Finlayson

Academic Editor

PLOS ONE

Journal Requirements:

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

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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 #3: No

**********

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 #3: 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 #3: No

**********

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: 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 #3: 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 #3: Annotation Summary of PONE-D-23-28616.pdf.

Note [page 15]: Abstract

Introduction: correct spelling of trail to trial

Methods: Change to “Diagnosis- Related” rather than "Diagnose"

Note [page 16]: Introduction

To make this more readable, I suggest that you put the definitions of morbidity followed by the stats, then the definition of complicated multi morbidity, then describe the situation in Denmark - with 10% having… etc.

The first 2 paras do not read well in the current format.

Later in the introduction, please state that you are in phase 3 of the MRC framework - if this is the case.

It is important that the introduction correlates with the outcomes of the study. The outcome of your study is a patient reported measure (at least your primary outcome). Therefore, when you comment on the current state of care for multi-morbid patients, please make reference to the literature which shows that existing patient reported outcomes are poor in this group.

Your other comments in the introduction regarding the ‘silo-ing’ of care or the lack of "effective care" are probably true, but this protocol is not designed to improve any of that. The primary outcome the study measures is the effect on patient reported outcomes.

I also think the introduction can be rewritten to improve flow and readability.

Note [page 22]: Methods - Qualitative Evaluation

There is repetition here regarding the guide for semistructured interviews. Please streamline, and mention the inclusions in your guide one place only. Articulate clearly the interviews that you will conduct as part of the qualitative process. Under each type of the interviews, list the questions you will consider in the semistructured interview. In its present form, there is a series of interviews mentioned and multiple "guides to interview" descriptions.

You also need to specify whether you will interview patients / HCPs who have been randomly allocated to standard care. Do you think this will be necessary so that you can draw good comparisons to your intervention group?

Note [page 22]: Outcomes.

Please see my earlier comment regarding writing an introduction that matches to the outcomes that you are studying in the current protocol. We need to show that the current literature demonstrates that patient reported outcomes are poor with the current models of care.

Note [page 25]: Discussion

Returning to my earlier comments, it is important that you mention in the discussion that the study seeks to improve patient experiences in particular. In its current form, you have spoken, generally about "improving care for patients" or "reducing burnout for GPs “. While both are laudable aims, the purpose of your study to improve patient-reported outcomes and you must talk about this in your discussion.

Note [page 27]: Source of potential bias

Please clarify this sentence: Patients recruited by their GP be more likely to participate when asked by a familiar healthcare professional whom they trust.

Principles of good clinical practice in research suggest that recruitment should not be undertaken by practitioners involved in the treatment of patients. Therefore, it would be wrong for patients to be asked to participate by a healthcare professional whom they are familiar with or trust.

All requests for participation in a clinical studies should be made by people who are not connected to the care of the patient so as to not introduce any unwanted pressure to participate. You are right in saying this is also a potential for bias.

I am sure you are aware of this but your sentence is misleading and needs to be clarified.

If, on the other hand, you do plan to recruit patients by invitations from their own health professionals, you must change this as it is not acceptable practice.

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Reviewer #3: Yes: Assoc Prof Rajesh Raj

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A patient-centred care model for patients with complicated multimorbidity: Protocol for a cluster randomised trial in general practice, municipalities, and hospitals

PONE-D-23-28616R2

Dear Dr. Lundstrøm,

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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Academic Editor

PLOS ONE

Additional Editor Comments:

Thank you for the revised article addressing the reviewers' feedback. There are just a few areas where inconsistency needs amending, where you have addressed feedback in one spot however not in others. Specifically,

- the aim in your abstract should include your primary outcome, i.e., effectiveness of xxx on ?outcome. The objective on p.4 does not match this aim, as 'treatment' is not your primary outcome, this should be patients' experience of quality care

- should economic outcomes be included in your secondary outcomes?

- in the sources of bias section, consider the reviewer's comments about the conflict of interest involved in relying on the patients' GPs to recruit, there is an ethical issue

- double check the grammar throughout, e.g. the pilot RCT WILL involve ....; DRGs should be Diagnosis (not diagnose as in abstract) etc.