PONE-D-20-11446

Family-centered music therapy - empowering premature infants and their primary caregivers trough music: A randomized, controlled pilot trail

PLOS ONE

Dear Dr. Menke,

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 reviewer pointed out several issues in methodology. These concerns need to be addressed carefully as methodology is of key importance in the acceptance criteria in the journal.

Please submit your revised manuscript by Dec 04 2020 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,

Olivier Baud, MD, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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

Reviewer #1: Yes

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

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

Reviewer #1: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study is original and aims to assess the combined effect of music therapy on premature infants, their mothers, and fathers. Previous studies have focused on assessing the effect of music therapy on premature infants and their mother only. Few studies assessed the impact on the fathers. Here, the paper is presenting the results of a pilot study for the implementation of a future bigger randomized and controlled trial.

General remark: the language needs to be verified carefully, there are some English spelling errors in the manuscript (title, line 62, line 526, line 544…).

1. Abstract:

In the results, the presentation is misleading as you wrote that durations of caffeine therapy, hospital stay, and NGO tube feed were shortened. In fact, reductions were not statistically significant, so please provide 95% confidence intervals around the reduction in days and/or p-values to moderate the findings. The reduction of stress factors in the parents from the treatment group only is also problematic as it does not say anything on the effect of intervention. You need to refer to the control group as well to compare the reduction to no intervention. Results presented in the abstract are generally very imprecise and provide false signals. The study does not provide some evidence that family-centered music therapy had an effect on the premature infant’s development, or on the parental stress factors.

2. Introduction:

Please revise your references list. It seems you have missed some recent and important works published by the team at the University hospitals of Geneva.

3. Methods:

• The investigators are not clear enough about what is primary versus secondary outcomes. They need to choose one key endpoint to be used to design the global study and to test their research hypothesis about a clinical important effect of a family-centered music therapy intervention in premature infants hospitalized at NICUs and their parents. The study will not be sufficiently powered to answer multiple research questions.

• The paragraph on the sample size estimation is not informative enough and it would need to be rewritten. How did you estimate that 50 parent-infant pairs would be necessary? There is no hypotheses presented here.

• Correlation coefficients should be interpreted using specific also subjective scales (for e.g. use Hinkle DE, Wiersma W, Jurs SG. Applied Statistics for the Behavioral Sciences. 5th ed. Boston: Houghton Mifflin; 2003), and not on p-values that are testing the null hypothesis rho=0.

• Normally, intention-to-treat analysis is performed in superiority trials, and completed by per-protocol analysis.

4. Results:

The general presentation of results is not informative enough and needs to be improved. The study shows no evidence for an impact of the intervention on the premature infant’s development. Moreover, the effect of the intervention was assessed by indirect indicators, such as the duration of caffeine therapy, the naso/oro-gastric tube feed, and the duration of hospital stay. The study results are inappropriately reported: there was no statistical difference between both study arms regarding the various primary outcomes assessed, nor regarding the parental factors (all p-values>0.05).

In the text, some useless results are reported and could be deleted, such as the values of test statistics, or the number of degrees of freedom for each statistical test performed.

The absence of evidence for differences in the comparisons of secondary outcomes between both arms does not mean that they are similar. This interpretation should be deleted.

All results on correlations are not correctly presented. The authors have copied the tables provided directly by the statistical software: correlation coefficients and p-values that are not informative here. Moreover, as usual the tables of correlations are symmetric, meaning that results are presented twice in the tables. Another way of presentation should be appropriately provided in a new version (figure? Informative table?). Finally, the interpretation of correlation coefficients is usually qualitative (various scales exist, e.g. in medicine )

5. Discussion:

Globally, the discussion could be shortened and more concise. No new results are expected in discussion (e.g. lines 480-487). Under limitations, the authors have mentioned some modification in the study design but it seems, this was not explained before? Based on the lack of evidence for an effect of family-centered music therapy provided by the study, the authors need to moderate their conclusion.

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6. 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.

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Reviewer #1: No

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PONE-D-20-11446R1

Family-centered music therapy - empowering premature infants and their primary caregivers through music: Results of a pilot study.

PLOS ONE

Dear Dr. Menke,

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 Mar 14 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Olivier Baud, MD, PhD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

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

Reviewer #1: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

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

Reviewer #1: 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: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In general, in this new version, the manuscript has improved in quality and the presentation of findings is better. However, the authors need to mitigate their interpretation of results (especially in the conclusion of the abstract) and formally referred to the fact that they have conducted a pilot study to assess its feasibility and to explore some variables measured among children, mothers and fathers to assess the effect of a family-centered music therapy intervention. The objective of current study was NOT to provide a final conclusion of an effect of the intervention as it is stated in this new version of the manuscript. The findings would need to be further confirmed in a formal and sufficiently powered randomised controlled trial. Finally, even if this version of the manuscript has improved, some important information on the description of the new statistical methods performed is lacking. Moreover, I would suggest that this new version should be evaluated by a biostatistician.

More specific remarks follow:

1) The justification for sample size is data-driven and it seems that it has been corrected to match with the numbers used.

2) There are many exclusions in the study that are not clearly described to my opinion. What were the reasons for the family to request destruction of their data after parental withdrawal? What do you mean by “For reasons of feasibility, this design was adapted to a pre-post design during the course of the study” and did you exclude 9 data sets because they were collected after the pre-post follow-up design? Please explain.

3) In this version, you have analysed the data using a principal component analysis (PCA) in the aim to evaluate the joined effect of several variables in a limited number of dimensions; an exploratory PCA was then performed to explore the existence of a latent variable explaining the underlying variables grouped in the dimensions. The description of the statistical methods should be revised by a biostatistician as I am not a specialist of the methods used here. The description of the statistical methods used for the PCA and exploratory PCA seems lacunar (you are supposed to describe how have you chosen the number of factors retained by a scree test, then you need to apply a rotation on the factors to interpret the patterns, etc…). Some methods are presented in the results section but would be more appropriately described in the statistical methods section of the manuscript.

4) Multiple comparisons (regarding the 6 individual primary outcomes) were performed between the two randomization groups but there is no correction for the inflation of alpha error. This should be modified in a new version of the manuscript.

5) English still needs to be revised in the new version of the manuscript (e.g. line 273 of the tracked changes version: “conducted” and not “conduced”).

6) For decimals, “.” should be used and not “,”. Please correct throughout the manuscript.

7) In randomised controlled trial, comparisons of baseline characteristics between the two randomisation groups should not use statistical tests but should only be descriptive. Any differences in baseline characteristics are the result of chance rather than bias (cf. CONSORT recommendations). Tests of baseline differences are not necessarily wrong, just illogical.

8) How did you explain this change in the selection of participants in the two groups? (Table 2). As already written, multiple test comparisons lead to false positives and this needs to be corrected using appropriate statistical methods. Why did you use one-sided t tests? Two-sided tests are generally preferred in the context of superiority trials.

9) More generally, the aim of current study was to assess its feasibility and to define which variables could be used to test for an effect of the family-centered intervention. The results provided here are interesting and they motivate the conduct of a new formal and sufficiently powered randomised controlled trial. However, throughout the manuscript, there is always some confusion on the objectives of this pilot study; interpretation of study findings are always overstated and do not refer to the investigators’ primary aim: to assess if such a study is feasible and if such an intervention could provide some signal on an effect of family-centered music therapy that needs to be formally tested in a bigger trial. This is misleading and the presentation and discussion on the results need to be mitigated in order to fit with the original objective of this pilot study. In the limitations, the reduction of study power due to exclusions should not be listed as again this was a pilot study where power is by definition not sufficient.

In summary, this new version of the manuscript still requires some revisions and I would recommend that statistical methods included in this new version should be assessed by a biostatistician.

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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.

Family-centered music therapy - empowering premature infants and their primary caregivers through music: Results of a pilot study.

PONE-D-20-11446R2

Dear Dr. Menke,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Olivier Baud, MD, PhD

Academic Editor

PLOS ONE

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