PONE-D-23-35122

Effectiveness of pain education on pain, disability, quality of life and self-efficacy in chronic low back pain: A randomized controlled trial

PLOS ONE

Dear Dr. Muthukrishnan, I hope this finds you well.

First of all, thank you for submitting your manuscript to PLOS ONE. I would like to congratulate you on your research. You aimed to gain an understanding of the effectiveness of pain education on pain levels, disability, quality of life, and self-efficacy in individuals with chronic low back pain. I kindly ask you to adjust the article according to my requests and the requests of the three reviewers. In this review, please mark your corrections and report the page and adjustment line. Besides, please:

—Change the title to: Effects of pain education on disability, pain, quality of life, and self-efficacy in chronic low back pain: A randomized controlled trial.

—Include keywords according to MeSH terms (https://www.ncbi.nlm.nih.gov/mesh/);

—The objective stated in your abstract is different from the objective stated in your introduction. Please correct this. The sentence describing the objective must be exactly the same in both;

—State a hypothesis in the introduction;

—The conclusion described in the abstract and the conclusion described after the discussion must be exactly the same;

—In the Methods (Data analysis) section, describe the classification used for the effect size (Cohen's d [https://pubmed.ncbi.nlm.nih.gov/37971135/]), since you reported it as n2 in Table 2.

—In Table 1, report the body mass (kg) and stature (cm);

—In Table 2, remove the description of within-group comparisons (not necessary for this RCT). Notice that your research question is answered by between-group comparisons.

—In Table 3, change p = 0.000 to p <0.001;

—Submit the database with the data in unanalyzed values (i.e., absolute values) as a supplemental file (Excel and English).

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Please submit your revised manuscript by Mar 07 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.

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We look forward to receiving your revised manuscript.

Kind regards,

André Pontes-Silva

Academic Editor

PLOS ONE

Journal requirements:

1. When submitting your revision, we need you to address these additional requirements.

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. In the online submission form, you indicated that [All the data supporting the findings of this trial is presented and the full dataset are available from the principal investigator on request.]. 

All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information.

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3. Please amend your authorship list in your manuscript file to include author Alagappan Thiyagarajan.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 

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

Reviewer #2: No

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

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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: No

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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: Yes

Reviewer #2: Yes

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: Thank you for the opportunity to review this article.

Below is my analysis of the manuscript.

Overall impression:

The study presents a solid scientific basis. There is significant thematic relevance and remarkable coherence in giving the context of previous literature, especially when considering the distinct cultural differences in each continent.

Main issues:

1) According to the journal's guidelines, including the trial or study's registration number in the abstract is essential.

2) The last paragraph of the introduction could be more concise, avoiding excessive repetition of terms.

3) Improving the description of the standard physiotherapeutic treatment is essential. It would be relevant to provide details of the physical assessments carried out and clarify whether all patients received the same type of treatment regarding sets, repetitions and weights. This is especially crucial considering the diversity in the fitness levels of the participating patients.

4) When writing the conclusion, it is important to exercise caution to ensure conciseness and a clear answer to the question raised in the introduction. The decision should be aligned with the results obtained, avoiding inappropriate wording.

Reviewer #2: This is an interesting study that is looking at the effect of pain education on pain intensity. However would benefit from some proof reading, as they are spelling mistakes in some places.

Major observation:

Primary outcomes measures are: The primary outcomes measures were related to the intensity of pain experienced during activities of daily life (ADL) and disability related to pain. Roland Morris Disability Questionnaire (RMDQ). The sample size is based on "mean score of pain intensity in chronic LBP patients (mean1 = 3.76, mean2 = 4.78, SD1 = 1.51, SD2 = + 1.91)". Its unclear whether this is a combination of of the two ADL and RMDQ - which by definition are co-primary endpoints. This needs to be reflected in the sample size, and the results as its confusing, there is reduction in disability and pain intensity.

In addition, if the question was addressing two co-primary endpoints? Then more information is required in terms multiplicity testing or not and why? Or pre-specified interpretations in terms of whether intervention works if one or both or either outcomes are observed to be clinically significant.

Some further suggestions;

1. In the introduction section, mention that the primary was at 6 weeks.

2. With the primary outcome, can the authors include the collection time points, i.e. in the data analysis section, the authors mention, post intervention. Is this at 6 weeks, or at follow-up time point?

3. As this is a randomised controlled trial, there needs to be distinction in terms of the analysis to reflect this. Its not clear what the main objective was.

Suggested to update the data analysis section,

-To include that as this an RCT, this will be reported in accordance to the CONSORT guidelines?

4. Why was lost to follow-up not accounted for in the sample size, or include a sentence to justify why not, i.e. by design because the intervention last 6 weeks, so were the researchers confident enough that participants would adhere?

5. It is not recommended to test baseline characteristics, any differences between baseline characteristics would be due to chance. - see this interesting article Correct Baseline Comparisons in a Randomized Trial Schober, Patrick MD, PhD, MMedStat*; Vetter, Thomas R. MD, MPH†

"Traditionally, baseline balance is assessed by a series of hypothesis tests comparing each baseline variable between the groups, and a nonsignificant result (P > .05) has commonly been considered to indicate baseline balance. This approach is flawed.2 First, all patients are randomly sampled from the same population, and any differences must be due to chance. It thus does not make sense to test hypotheses of group differences at baseline. Second, hypothesis tests are greatly affected by sample size. In a smaller trial, marked differences between the groups can be nonsignificant, whereas in a larger trial, negligible differences could be significant."

6. This sentence is incomplete "Unadjusted mean (SD), and standard error (SE) of the mean difference (MD) between the groups with associated 95% confidence interval and p-value were computed for the outcome measures at baseline and post-intervention"- using what statistical approach/model?

7. The authors jump straight to logistic prognostic model - which is not clear whether this was separate objective. The most appropriate approach would be better to be explicit as to whether the outcomes were analysed with the pre-specified baseline characteristics for assessing the treatment effect.

The statistical analysis of prognostic model should be differentiated from the research question (primary) and secondary (which are questions assessing the effect of the intervention) - otherwise its confusing.

8. How was missing data handled- this is not mentioned?

9. Also in the statistical analysis section, mention when the SAP was drafted etc.

10. How was adherence/compliance assessed

11. Table 1 - add percentage for gender (male and female).

12. There is imbalance in terms of occupation, interestingly more housewives in the control group.

13. Additional information is missing in the randomisation section include allocation ratio.

14. Figure 2 - put units on y-axis (e.g mean score difference

15. Discuss limitation in terms of generalizability, as this was in one single centre?

Reviewer #3: I appreciate the opportunity to review this study. The authors conducted a randomized controlled trial aiming to assess the effectiveness of pain education on pain levels, disability, quality of life, and self-efficacy in individuals with chronic low back pain (CLBP). The manuscript is well-written and detailed, indicating a significant investment of time and effort. I will provide specific comments on the manuscript below.

Abstract:

-  I recommend revising the aim as follows: “This randomized controlled trial aimed to evaluate the effectiveness of pain education on pain levels, disability, quality of life, and self-efficacy in individuals with chronic low back pain (CLBP)”.

Introduction:

- It is crucial to include references to previous studies that have assessed the effect of PNE in patients with CLBP. Provide a summary of their findings and highlight the novelty of the present study.

- The introduction should include the scientific background of the topic and an explanation of the rationale.

The authors need to clearly state the hypothesis of the study.

Methods:

Reference “Figure 1” as the flow diagram in the manuscript.

If there were any modifications to the methods after trial registration, specify them.

Provide a detailed description of the intervention called “standard physiotherapy." It would be important not only for transparency but also to offer valuable information for future studies.

Assess and report on the blinding procedures. How can the authors ensure that appropriate blinding is achieved?

Sample size:

Recommend recalculating the sample size, especially considering the Roland-Morris Disability Questionnaire (RMDQ) as a primary outcome. Address the baseline differences between groups, as comparing groups with distinct profiles is a serious concern.

Examine the differences between groups for specific variables like smokers and RMDQ scores. Clarify how these differences were managed in the analysis.

Discuss how the authors addressed the potential bias introduced by one group receiving more treatment, potentially influencing their improvement compared to the control group. Acknowledge this as a potential limitation.

Prognostic model:

Clarify why the prognostic model was not explicitly stated as the aim of the study.

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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.

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: 

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[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-23-35122R1Effects of pain education on disability, pain, quality of life, and self-efficacy in chronic low back pain: A randomized controlled trialPLOS ONE

Dear Dr. Muthukrishnan, I hope you are well.

Please review your article and submit it for final consideration.

Minor revisions:

1- Sample Size Calculation: Indicate the statistical testing method used for the sample size calculation. Perhaps it is the t-test.

2- Data analysis section:

a. Typographical error: Student’s t-test.

b. State the underlying covariance structure used in the linear mixed model and the criteria for selecting it.

3- In addition to the mean age, include the corresponding standard deviation. Throughout the manuscript when stating means, provide the corresponding standard deviations.

4- Table 1: In the statistical methods section, state and describe the use of all statistical methods.

a. Indicate the statistical testing method used for comparing categorical data.

b. State and describe the use of logistic regression modeling.

5- To assist in the review process, add line numbering to the document.

• Indicate which changes you require for acceptance versus which changes you recommend
• Address any conflicts between the reviews so that it's clear which advice the authors should follow
• Provide specific feedback from your evaluation of the manuscript

Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact.

For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

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Please submit your revised manuscript by May 23 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,

André Pontes-Silva

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. 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)

Reviewer #4: (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: Yes

Reviewer #4: Yes

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

Reviewer #1: Yes

Reviewer #4: 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: Yes

Reviewer #4: 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

Reviewer #4: 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: Thank them for promptly responding to the suggested corrections and demonstrating their commitment. The adjustments made to the sections, especially the methodology, contributed significantly to strengthening the argument and clarity of the text.

I encourage the authors to consider the observations made for future research.

Reviewer #4: This two-arm randomized controlled clinical trial aimed to assess the effects of pain education on pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals with chronic low back pain as assessed before and after 6-weeks of intervention. Post-intervention scores significantly differed at post intervention between the groups in the areas of disability, pain intensity, and well-being index, where the intervention group had better results.

Minor revisions:

1- Sample Size Calculation: Indicate the statistical testing method used for the sample size calculation. Perhaps it is the t-test.

2- Data analysis section:

a. Typographical error: Student’s t-test.

b. State the underlying covariance structure used in the linear mixed model and the criteria for selecting it.

3- In addition to the mean age, include the corresponding standard deviation. Throughout the manuscript when stating means, provide the corresponding standard deviations.

4- Table 1: In the statistical methods section, state and describe the use of all statistical methods.

a. Indicate the statistical testing method used for comparing categorical data.

b. State and describe the use of logistic regression modeling.

5- To assist in the review process, add line numbering to the document.

**********

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 #4: No

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[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.

Effects of pain education on disability, pain, quality of life, and self-efficacy in chronic low back pain: A randomized controlled trial

PONE-D-23-35122R2

Dear Dr. %Muthukrishnan%, I would like to thank you for your responses and corrections. 

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,

André Pontes-Silva

Academic Editor

PLOS ONE