PONE-D-25-08339Effect of Health Education Intervention on Treatment Adherence and Health Status in Patients with Chronic Obstruction Pulmonary Disease: A Random Control TrialPLOS ONE

Dear Dr. Thong,

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.

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ACADEMIC EDITOR: This study has the potential to provide valuable evidence on health education interventions and outcomes for COPD in Vietnam, an area that is currently lacking research. The topic is of interest. However, please ensure that all comments from the reviewers are addressed, particularly the methodology section, which needs further refinement.

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Please submit your revised manuscript by May 05 2025 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,

Thien Tan Tri Tai Truyen, M.D.

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

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: 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

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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

Reviewer #2: 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: COPD is a major global health burden, especially in low- and middle-income countries. Your study addresses a crucial aspect of COPD management—treatment adherence—by evaluating a health education intervention.

Following are my comments:

1. Methodological Concerns

A. Selection of Control Group

The control group was selected from a different hospital (Da Nang Lung Hospital), while the intervention group was from C-Da Nang Hospital.

Differences in hospital protocols, healthcare provider behavior, and patient populations could introduce confounding variables.

Ideally, both groups should be drawn from the same pool and randomized within the same hospital to minimize systematic differences.

B. Sample Size Justification

i. The calculation assumes an expected adherence increase from 50% to 85%, which is a very optimistic improvement.

This large effect size may not be realistic and could lead to underpowered results if actual improvements are smaller.

ii. High Attrition Rate Consideration

While the study factored in a 30% dropout rate, 100% of patients completed the intervention, which is highly unusual for behavioral studies.

A discussion on how dropout bias was avoided would strengthen credibility.

C. Intervention Implementation and Measurement Bias

i. Self-Reported Adherence Measurements

The adherence assessment (TAI-10 and breathing exercise checklist) is based on self-reporting, which is prone to social desirability bias and recall bias.

Patients may over-report adherence, especially when aware of being monitored.

Consider adding an objective measure, such as electronic monitoring devices for inhalers or video-confirmed breathing exercises.

ii. Blinding of Outcome Assessors

The research team who provided the intervention also assessed adherence outcomes, which may introduce observer bias.

Ideally, assessors should be blinded to the intervention group to minimize bias in adherence reporting.

iii. Lack of Long-Term Follow-Up

The study only measures adherence and health status at three months post-intervention.

A longer follow-up (e.g., 6 or 12 months) would provide insights into whether adherence improvements are sustained over time.

2. Statistical and Data Reporting Issues

A. No Effect Size Reporting

While statistical significance (p-values) is provided, effect sizes (e.g., Cohen’s d for t-tests, odds ratios for categorical outcomes) should be included to quantify the magnitude of changes.

Reporting confidence intervals (CIs) would improve result interpretation.

B. Comparison of Airway Obstruction (FEV1 Stages)

The study claims a positive shift in airway obstruction stages, but no statistical significance (p > 0.05) is reported.

This suggests the improvement could be due to chance rather than the intervention.

More detailed subgroup analysis is needed to explore trends in different severity groups.

3. Literature Review and Framing Issues

A. Limited Discussion of Existing Multicomponent Interventions

The introduction highlights previous studies focusing on either medication adherence or breathing exercises but does not discuss combined interventions.

Are there prior integrated adherence interventions for COPD that your study builds upon? A more thorough review would strengthen justification.

B. GOLD 2024 Citation Needs More Context

The study references GOLD 2024 but does not elaborate on how the intervention aligns with GOLD-recommended strategies for adherence improvement.

Explicitly linking your intervention elements to GOLD recommendations would add clarity.

C. More Critical Analysis of Vietnam-Specific Barriers

The study emphasizes Vietnam's limited research on COPD adherence but does not explore country-specific barriers (e.g., healthcare accessibility, cultural beliefs, financial constraints).

A deeper discussion on why adherence is particularly low in Vietnam would provide better context.

4. Ethical and Practical Considerations

A. Potential Coercion in Phone Call Participation

Patients were called three times if they missed a session, which may feel coercive.

Clarify if patients were free to decline participation without consequences.

B. Lack of Standardization in Group Calls

Patients were reminded about adherence via group calls and personal calls, but individual responses may have been influenced by peer pressure.

Were all group calls structured identically? Standardizing these interactions would enhance consistency.

Clarity & Conciseness

5. Discussion

The discussion is lengthy and repetitive in certain areas, particularly in emphasizing adherence statistics multiple times. Condensing these sections can enhance readability.

Some sentences are complex and need restructuring for better flow. Example:

“In fact, adherenting inhaler frequent and technique are closely related but quite independent concepts and can be influenced by different factors [26].”

Suggestion: “While frequent inhaler use and correct technique are related, they are distinct concepts influenced by different factors [26].”

6. Scientific Rigor & Interpretation of Results

A. The interpretation of airway obstruction improvement could be overstated, as the difference in obstruction severity (stage 3 to stage 2) was not statistically significant (p > 0.05).

Consider rewording to acknowledge that while a positive trend was observed, the results do not conclusively prove a long-term change in lung function.

B. Short-Term Nature of Study

The discussion acknowledges the 3-month limitation, but a more detailed recommendation for longitudinal follow-up would strengthen the argument.

Suggestion: Consider whether behavioral adherence improvements persist beyond 3 months or if patients require continued reinforcement.

C. Generalisability Issues

The discussion correctly states that the findings apply only to stable COPD patients. However, a more nuanced discussion on how this intervention might work in severe COPD or hospitalized patients would be valuable.

Your study is well-structured, methodologically sound, and addresses a critical issue in COPD management. However, some methodological concerns—selection bias, self-reported adherence, lack of long-term follow-up, and absence of blinding—should be addressed to enhance reliability.

Reviewer #2: The present is an interesting paper. Some issues should be added

1) primary end point should be clearly stated in the abstract

2)probably for a typo abstract is double reported

3) sample size in the methods>a reference should be added for 50%

4) it should be added if randomization was performed through block and how many patients

5)normal distribution should be checked for

6) due to the reduced sample size, do authors think that multivariate analysis may be of help

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Reviewer #1: No

Reviewer #2: Yes:  Fabrizio D'Ascenzo

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Effect of Health Education Intervention on Treatment Adherence and Health Status in Patients with Chronic Obstruction Pulmonary Disease: A Random Control Trial

PONE-D-25-08339R1

Dear Dr. Thong,

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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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,

Thien Tan Tri Tai Truyen, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

Reviewer #3: All comments have been addressed

Reviewer #4: 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: (No Response)

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: (No Response)

Reviewer #2: (No Response)

Reviewer #3: 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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: 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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: 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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: I wasn't involved in the first round of peer-review, but I agree the authors did a good job addressing the reviewers' concerns, and provided explainations for limitations of the study. In all, I believe the manuscript is good for publication.

Reviewer #4: This is an interesting and relevant manuscript that aims to evaluate the effectiveness of the health education intervention with the purposes of evaluating the effectiveness of a health education intervention on treatment adherence behaviour of COPD outpatients

The research idea is fairly novel, and the methodology used make this study interesting and provides important conclusions with a potential impact in clinical practice and in health care planning and organization.

The study design is well structured and follows the construction recommended for a randomised control trial.

The discussion is well structured, pertinent, and clear and the conclusions are relevant and based on the results.

Some questions raised by previous reviewers were methodically answered by the authors in an accurate way.

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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

Reviewer #2: Yes:  Fabrizio D'Ascenzo

Reviewer #3: No

Reviewer #4: No

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