PONE-D-24-58527Assessment of drug-related problems among breast cancer patients in a cancer specialty center in NepalPLOS ONE

Dear Dr. Sah,

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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Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

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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

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

Reviewer #1: Yes

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: • The title is clear and concise, accurately reflecting the study's focus on drug-related problems (DRPs) among breast cancer patients in Nepal.

• The abstract provides a good summary of the study, including the background, methods, results, and conclusion. However, it could benefit from a brief mention of the study's limitations.

• The introduction could be enhanced by providing more detailed information on previous studies related to DRPs in breast cancer patients, particularly in similar settings.

• The sample size calculation is explained, but the rationale for choosing a 50% prevalence rate could be clarified. Additionally, more information on how patient interviews were conducted and how data accuracy was ensured would be beneficial.

• The rationale for choosing a cross-sectional design could be elaborated. Additionally, more details about the hospital's patient population and its relevance to the study could provide better context.

• The manuscript could benefit from a more detailed description of how patient confidentiality was maintained and any measures taken to ensure ethical standards were upheld throughout the study.

• The exclusion criteria are not mentioned and should be included to provide a complete understanding of the study population.

• More details on how patient interviews were conducted, including the interview process, duration, and any training provided to the interviewers, would enhance the transparency of the data collection process. Additionally, the manuscript should describe how data accuracy and consistency were ensured.

• The manuscript could benefit from a more detailed explanation of the statistical analysis, including any software used and the rationale for choosing specific statistical tests. Additionally, the manuscript should discuss how missing data were handled and any sensitivity analyses performed.

• The manuscript should provide more details on the criteria used by the oncologists to verify DRPs and how discrepancies between the two oncologists were resolved.

• The Methods section should explicitly mention potential limitations related to the study design, data collection, and analysis. For example, the use of a single center and the potential for selection bias should be discussed.

• To enhance the rigor and transparency of the study, the manuscript should provide more detailed justifications for methodological choices, describe the data collection and verification processes in greater detail, and explicitly discuss potential limitations.

• The results section could be improved by providing more detailed statistical analysis, including confidence intervals for key findings. Additionally, a more in-depth discussion of the types of DRPs and their potential impact on patient outcomes would be valuable.

• The discussion could be strengthened by exploring potential interventions to reduce DRPs and improve patient outcomes. Additionally, the study's limitations should be discussed in more detail, including potential biases and the generalizability of the findings.

• The conclusion could be enhanced by providing specific recommendations for future research and clinical practice.

• Ensure all references are formatted consistently according to the journal's guidelines.

• To enhance the manuscript, consider providing more detailed statistical analysis, discussing the study's limitations more thoroughly, and offering specific recommendations for clinical practice and future research.

Reviewer #2: This is an interesting study and the authors have done a good job on its execution. Please find some of my comments for better outcome for manuscript:

Introduction section:

-The whole manuscript may be revised for clarity and flow. Redundant concepts/ideas need to be revised (Line 66-68 and 70-72: pretty much share the same idea of patients being susceptible and a lack of local research).

-Line 69-70: Consider reframing this sentence. The sentence is phrased awkwardly as of now.

-The authors may emphasize the rationale of this study more in the last section of the Introduction.

Method Section:

-Since the sample size is calculated, a clear justification for the use of the purposive sampling method (non-probabilistic sampling method) needs to be made. Was it because of a smaller population group, feasibility issues, or was it something else?

-DRP identification by two individuals was a great approach, but how was any discrepancy among them resolved? Adding some information about the management of conflicts in case of occurrence would add value.

-Explain the terms used in the formula for sample size calculations. It is not well formulated in the current version.

-If possible, information on which variables (sociodemographic or clinical variables) were tested for association with DRPs in the method section itself would add better flow to the reader.

Results and discussion:

-The results and discussion sections are well formulated. Make sure the percentages used in the brackets are aligned with the one mentioned in the result writing and tables.

-Line 135: 91 or 92 patients?

Conclusion:

-Line 245: May be rephrased by removing the word ‘significant’ since this is not regarding any statistical test, but rather just the frequency.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-24-58527R1Assessment of drug-related problems among breast cancer patients in a cancer specialty center in NepalPLOS ONE

Dear Dr. Sah,

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.

Reviewer 1 has highlighted some concerns. Please try to address these concerns in the next revision. 

Please submit your revised manuscript by Sep 20 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.

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,

Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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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 #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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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: Yes

Reviewer #2: (No Response)

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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 #2: No

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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: General Structure and Rationale

1. Clearly state whether the primary goal is to estimate the prevalence of DRPs or explore associated risk factors. The current phrasing oscillates.

2. The rationale is sound, but why was this particular center (BCH) chosen? More details on selection rationale beyond "governmental and accessible" would help.

3. The manuscript claims to be the first in Nepal, but doesn't reference enough regional studies to support this. Could there be unpublished or gray literature?

4. There is no reflection on how temporality or causality is limited in the discussion; should be explicitly acknowledged.

5. Repetition of phrases like “increased DRPs” and “pharmaceutical care” reduces clarity. Consider more varied academic phrasing.

Abstract and Keywords

6. The abstract includes excessive numerical detail and minor results; consider summarizing key findings more concisely.

7. Add more specific terms such as “PCNE classification,” “Nepal,” or “oncology pharmacy” for better indexing.

Methods

8. Purposive sampling is a major limitation—state how selection bias was minimized and how representativeness was ensured.

9. The initial assumption of 50% prevalence is fine for conservative estimates, but justify why 3 months of data was chosen.

10. Was the data collection tool (based on PCNE) piloted or validated in this setting?

11. Why exclude patients who returned for further chemo? This could skew the sample toward early-stage patients.

12. More information is needed on how disagreements were resolved between oncologists. What was the inter-rater reliability?

13. Were adjustments made for potential confounders (age, comorbidities, etc.)? No multivariable analysis was conducted.

14. Consider at least a basic sensitivity test for key findings due to small sample size.

15. When exactly was DRP assessed—before, during, or after chemo cycles? Clarity would improve reproducibility.

16. How were ADRs classified—was any scale (Naranjo, CTCAE) used?

17. IRB approval is cited but mention if this study was registered on any clinical trial registry.

Statistical Analysis

18. Only chi-square and Fisher’s exact tests were used. Consider logistic regression to control for multiple variables simultaneously.

19. Absence of CIs undermines the robustness of prevalence and association measures.

20. Effect sizes (odds ratios, relative risks) are not reported, which makes interpretation of significance less informative.

21. Given many comparisons, were p-values adjusted to account for Type I error?

Results

22. The 98.9% DRP prevalence is alarmingly high. Is this comparable to similar populations, or could it reflect overclassification?

23. Were any participants excluded due to incomplete data? This is not discussed.

24. At one point, 104 DRPs in 91 patients are discussed—make clearer what proportion had multiple DRPs.

25. Table 1 includes too many levels—merge low-frequency categories (e.g., occupation).

26. Reference is made to a figure not shown in the review—ensure figures are labeled and included.

Discussion

27. Discussion draws mainly on Ethiopia and Kenya—are there more LMIC examples to support cross-cultural relevance?

28. Phrases such as “DRPs were caused by…” should be tempered due to study design limits.

29. Expand on why timing/dosing issues are so prevalent—does this point to health literacy gaps, regimen complexity, or system failures?

30. High number of drugs prescribed is noted—discuss whether this is guideline-recommended or potentially excessive.

31. Many intervention ideas are proposed, but no feasibility or pilot data are cited—frame as hypotheses or recommendations.

32. Good point raised—but explain if Nepal’s national PV system supports hospital-based units practically.

33. Does BCH have a formal reporting mechanism for ADRs? Mention if findings have been/will be reported there.

Language and Style

34. Past and present tenses are used inconsistently throughout the methods and results.

35. Phrases like “it might be difficult to generalize the findings” occur multiple times. Use once and move on.

36. Numerous minor grammatical errors (e.g., "do not explain" should be "does not explain")—recommend copyediting pass.

37. "Protein powder," "immunity booster"—provide generic names or ingredient lists to ensure scientific precision.

38. Terms like “TAC” and “FEC” appear before being defined—define all chemotherapy abbreviations upon first use.

Conclusion

39. Statements about fulfilling National Cancer Control Strategy goals are too broad. Keep the focus on DRP assessment and interventions.

40. Mention specific designs (e.g., prospective cohort, pharmacist-led intervention RCTs) instead of vague calls for “more studies.”

Reviewer #2: So far my comments has been addressed but I highly recommend the authors to use some sort of tools to improve the understanding of the sentences in manuscript. I still stick with the comment for revising the writing/structure of the sentences throughout the manuscript to make it unambiguous with appropriate flow.

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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: Yes:  Sunil Shrestha

Reviewer #2: 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.

Assessment of drug-related problems among breast cancer patients in a cancer specialty center in Nepal

PONE-D-24-58527R2

Dear Dr. Sah,

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,

Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

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 #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 #2: Yes

**********

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

Reviewer #2: Yes

**********

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 #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 #2: 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 #2: The revised manuscript looks good for the publication. However, I notice no confidence interval reported. Only p-values are reported. CIs might give a better sense of the precision of the findings to the readers.

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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 #2: No

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