PONE-D-22-27339Integration of primary contact physiotherapists in the emergency department for individuals presenting with minor musculoskeletal disorders: Protocol for an economic evaluationPLOS ONE

Dear Dr. Gagnon,

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 Jul 22 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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

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

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

We look forward to receiving your revised manuscript.

Kind regards,

Joshua Robert Zadro, PhD

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. We note that you will be accessing administrative databases for data collection for your study. Please clarify which databases will be accessed and whether you have obtained the necessary ethics approval or permission to access these databases. Furthermore, please clarify whether these databases are anonymized.

3. Thank you for stating in your Funding Statement:

“Part of the data that will be used in this study were acquired during a project that was supported by the CHU de Québec – Université Laval, subsidies from LJH and KP and a clinical research scholarship awarded to one of the CHU de Québec collaborators by the Fondation du CHU de Québec for the multidisciplinary council of the CHU de Québec – Université Laval . RG received scholarships from the Canadian Institute of Health Research (CIHR; https://cihr-irsc.gc.ca/e/193.html), the Fonds de recherche du Québec – Santé (FRQ-S; https://frq.gouv.qc.ca/sante/), the Unité de Soutien SSA – Québec (https://ssaquebec.ca/), the Ordre professionnel de la physiothérapie du Québec (OPPQ; https://oppq.qc.ca/), the Centre interdisciplinaire de recherche en réadaptation et intégration sociale (Cirris; https://www.cirris.ulaval.ca/) and Université Laval (https://www.fmed.ulaval.ca/). JRG, SB and FD are FRQ-S Research Scholars. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

4. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Additional Editor Comments (if provided):

Thank you for your patience Rose and apologies again for the delay. The reviewers are generally positive about the protocol but there is more detailed needed in numerous places. Please pay careful attention to the reviewers comments when revising your paper.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

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 #1: Yes

Reviewer #2: Yes

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 #1: This work has three objectives: to compare the average cost, to evaluate the ICER, and to estimate the ICER of the models of interest, which would be the combinations of physiotherapist and ED physician, ED physician alone, or physiotherapist alone.

1. Why only objective 3 consider the model with the group of primary contact physiotherapist management alone?

2. Authors propose to use decision tree for objective 2. However, tree is well-known to be overfitting. Please provide the information how this will be avoided in the analysis plan.

3. Authors argued to impute data using the Missing not at random approach. Please be specific how this will be implemented, especially if it’s not at random, what assumptions the authors will make? And whether it is reasonable in practice?

Reviewer #2: Just clarify if the total sample size is 78 or as read in lign 49-50 that data are collected during a randomized clinical trial (n=78) as well from CHU Québec administrative databases .Are they the same

Do you have an estimate of the number of men and women for the subgroup analyses.What about the lack of power if a group is too small?

Reviewer #3: Thank you for the opportunity to review this interesting work examining the cost-effectiveness of an physiotherapy led intervention in the emergency department setting. The ability to conduct an economic evaluation using clinical trial data associated with an allied healthcare intervention in the emergency department is not that common in the literature as outlined in the introduction of the paper. The structure of the paper is well organized however further clarification is required and along with the provision of more details about the methods prior to being suitable for publication.

Major comments

1. Although the manuscript describes a protocol for an economic evaluation, it would be of benefit to follow the CHEERS 2022 reporting guidance for economic evaluations. This is primarily applicable to the items outlined in the checklist associated with reporting of Methods (items 4-21).

Husereau, D., Drummond, M., Augustovski, F., et al. & CHEERS 2022 ISPOR Good Research Practices Task Force (2022). Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. BMJ (Clinical research ed.), 376, e067975. https://doi.org/10.1136/bmj-2021-067975

2. Further description in the methods is needed to outline how the costing will be completed associated with the Recommendation and use of services and resources at baseline and 1- and 3-month follow-up visits as outlined in Table 3 of your published clinical trial paper pg. 854. How will uncertainty associated with these costs be addressed in the model? Also from Table 3 are any of the consultation with other professional further physiotherapy appointments with outpatient public or private healthcare providers? How will these visits be costed out?

3. With respect to Objective 3 in the manuscript please expand on the rationale for considering how a short-term ED physiotherapist intervention is to have a clinical impact and effect an individual’s healthcare resource utilization and costs over a two-year period. It is stated in the manuscript that follow-up for studies with similar interventions have had follow-up periods up to 2 years. What are some of the findings of these papers and their limitations that need to be considered associated with your utilization of a 2-year time horizon for the economic evaluation.

4. Please justify further why only a societal perspective was used for the analysis. It would seem to be important for this evaluation to provide the perspective of the health system (i.e. the hospital and the provincial payers) as well as just the patient perspective for out of pocket expenses and potential time off work.

5. Please provide further details regarding which specific CHU de Quebec – UL administrative dataases will be used and which public databases will be used. Do you have permission for the study to use hospital level administrative inpatient and outpatient reporting systems?

6. Further details regarding the calculation of dis-utility from baseline to 1 month and 3 months is required. It states in the manuscript that mean-utility scores will be used. Will you be determining the utility values using Area Under the Curve analysis for each patient? Using just the calculated mean values at each time point may not reflect the within patient changes in quality of life.

Minor comments

1. Please provide updated Figures 2 and 3. They did not upload appropriately in the pdf image and are not readable.

2. What is the cycle length associated with the Markov Model?

3. Further description of the anticipated sensitivity analyses.

4. Consider discussing the challenges faced so far with the development of the protocol and analysis plan.

**********

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

Reviewer #2: No

Reviewer #3: Yes: James Bowen

**********

[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.

Integration of primary contact physiotherapists in the emergency department for individuals presenting with minor musculoskeletal disorders: protocol for an economic evaluation

PONE-D-22-27339R1

Dear Dr. Gagnon,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Joshua Robert Zadro, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

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

Reviewer #1: Yes

Reviewer #3: Yes

**********

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

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #3: 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

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 #1: Yes

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 #1: thanks for the response. all comments have been successfully addressed and I have no further comments.

Reviewer #3: Thank you for addressing the comments of the reviewers. The methodology associated with the economic evaluation are more fully described in the revised manuscript.

**********

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

Reviewer #3: Yes: James M. Bowen

**********