-->PONE-D-25-20506-->-->Identifying robust predictors of treatment response in trauma-affected refugees: results from a randomised controlled trial-->-->PLOS ONE

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PLOS ONE

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2. Thank you for stating in your Funding Statement:

[The RCT was supported by grants from TrygFonden (JC, grant number 120354) and Fonden til Lægevidenskabens Fremme (HS, grant number 16-319).]

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[The RCT was supported by grants from TrygFonden and Fonden til Lægevidenskabens Fremme (Foundation for Promotion of Medicine).]

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Reviewers' comments:

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-->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

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: Yes

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

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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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: This manuscript presents data analysis from a randomized control trial (RCT) that aims to identify robust predictors of treatment responses, specifically, posttreatment score differences in PTSD symptoms, among trauma-affected refugees in Denmark. The topic is of paramount importance in global public health, given the global burden of refugees. The study was registered as a RCT (with a valid NCT number), and was approved by the respective IRB/Ethics Committee. Some other (statistical) comments were also provided.

1. Methods:

Methods reporting need some work. In the paper, the authors pointed to the reader to look into previous published work on the proposed RCT. However, to maintain the continuity of this current work, some additional effort is needed to briefly reiterate some of the design aspects of the study published in a previous work within this paper.

Specific comments:

(a) For instance, clearly mention the groups that subjects were randomized into. Also, the randomization and allocation concealment should be made very clear (they are NOT the same thing); the trial staff recruiting patients should NOT have the randomization list. Randomization should be prepared by the trial statistician, and he/she would not participate in the recruiting.

(b) Some details on the randomization is needed, which might be already available in the published work. I would advise the authors to put some sentences in that regard with brevity.

(c) Sample size: The sample size/power statement should also be reiterated, with specific reference to the primary outcome measure (posttreatment score differences).

(d) Statistical Analysis Plan:

(d1) A major part of the analysis focuses on regression techniques, which are valid under strong Gaussian assumptions of the errors. Did the authors confirm that Gaussian assumptions when fitting the multiple regression with the response (score differences) were valid? If not, they need to seek alternative methods.

(d2) What's the plan for handling missing values in the design?

2. Results & Conclusions:

(a) The authors should check that any statement of significance should be followed by a p-value in the entire Results section. Otherwise, the Results section look OK; it's pretty straightforward.

(b) Conclusions should state that the current findings are ONLY based on the random samples derived from the refugees entering Denmark. For a comprehensive yet robust evaluation of the predictors, they should allude to future studies involving multiple regions/countries, with much larger sample sizes.

Reviewer #2: This replication study robustly confirms several previously reported predictors of refugee treatment response—especially younger age, lower baseline pain, and five “psychotherapy-readiness” items. Analytic methods are sound. I have some comments for the paper.

Major concerns

1. Methods

Multiple Testing: Discuss risk of false positives and use using p < 0.05 without adjustment.

2. Results

Direction of Effects: Explicitly state whether each predictor is linked to greater or lesser symptom improvement (e.g., refugee status predicted less PTSD change; 5–10 years impairment predicted poorer depression outcome).

3. Results

Table 2 Accuracy: Show denominators for each percentage so figures match actual N. For example, Migrant status / Refugee / 165 / 75.69. N is 218, not 219.

Minor concerns

1. Correct the typos such as “in-depht” to “in-depth” and “1th of June” to “1st of June” in the Methods. Remove stray commas and semicolons as noted (e.g. “we have previously published seven papers identifying different predictors” rather than “predictors of treatment response, (17, …)” which currently has a comma typo).

2. Since the predictor index involves clinician ratings, consider mentioning whether multiple raters were involved and if any training or consistency checks were in place. In the Discussion, you rightly plan to improve inter-rater reliability in future – that’s good. Even a brief mention of current inter-rater agreement (if known) would be useful for readers to gauge the quality of those measures.

3. Use consistent terminology for the CTP predictor index / psychotherapy-readiness construct. For example, if introducing it as the “CTP predictor index” in Methods, later refer to it simply as “predictor index” or psychotherapy readiness index (if you choose that term) rather than varying the name. Similarly, when referring to change in scores, consider stating “improvement (reduction in symptoms)” to remind the reader that a decrease in HTQ/HAM-D is an improvement.

Reviewer #3: Comments: Thank you for giving me an opportunity to review this important study that identifies robust predictors of treatment response in trauma2 affected refugees based on previous randomized studies. Based on the growing number of refugees with mental health problems, the authors are commedable for coming up with this innovation.

Please see below my minor comments.

Can the authors expand on their recommendations to take care of “ none modifiable risk factors”. In the context of refugee settings and cumulative trauma, personal guilt, maladaptive coping behavior of rumination such as the survivors’ persistent thoughts on how justice or revenge against the perpetrators could be achieved perpetuate various mental health comorbidities

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Comments to Authors.pdf

Identifying robust predictors of treatment response in trauma-affected refugees: results from a randomised controlled trial

PONE-D-25-20506R1

Dear Dr. Hinuga Sandahl,

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.

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Kind regards,

Mu-Hong Chen, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewer #1:

Reviewer #2:

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: All comments have been addressed

Reviewer #2: All comments have been addressed

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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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

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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: (No Response)

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 Response)

Reviewer #2: Yes

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-->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: (No Response)

Reviewer #2: (No Response)

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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.

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Reviewer #1: No

Reviewer #2: No

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