PONE-D-21-27919Administering of oral dosage forms of medicines to children in a resource limited settingPLOS ONE

Dear Dr. Nadeshkumar,

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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We look forward to receiving your revised manuscript.

Kind regards,

Vijayaprakash Suppiah, 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: 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: 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: 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: Thank you for the opportunity to review your manuscript regarding safe and appropriate administration of oral formulations to infants and young children.

Here are my comments:

1. English is a tricky language. Your manuscript would be greatly improved by having a native English speaker review and revise the wording and sentence structure. For example, administration vs administering is the appropriate word in the title;

Consider changing to: Administration of oral medication dosage forms to children in a limited resource setting (better flow in common English language)

2. Please define all abbreviations upon first use e.g. ODF, and terms such as safe water, well water, and tube well water in the first part of the paper and risks of unsafe water to dissolve oral medications.

4. The procedure for selection of the prescriptions for review in the study is unclear. This section requires revision with clear inclusion and exclusion criteria, listing the dates of the study period, and ages of patients 0- 12 years?

Was the medication prescribed for a minimum of 1 month or < 1 month? Please clarify in procedure.

5. Was adherence to the prescription evaluated? - goal of oral dosage forms that can be easily administered and tolerated, correct?

6. Was there a difference in patient practice if they had one child vs > 1 child? Would be interesting to compare these groups

7. Were all oral medications included in this study able to be safely crushed? Please refer to ISMP list Medications that should not be crushed: updated in 2021 https://www.ismp.org/recommendations/do-not-crush

8. Did you collect demographics beyond age of children? How about diagnoses, area of residence (urban vs rural?), etc

9. Moving beyond descriptive statistics, consider regressions examining factors associated with appropriate oral dosage administration for a more meaningful impact on practice. Which authors were involved in the analysis?

10. Discussion, regarding need for printed education for parents (is there a literacy issue?), how about "teach back" method

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Reviewer #1: Yes: Victoria Tutag Lehr, Pharm D Professor Pharmacy Practice Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit MI 48201

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PONE-D-21-27919R1Administration of oral dosage forms of medicines to children in a resource limited settingPLOS ONE

Dear Dr. Nadeshkumar,

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 Aug 18 2022 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:

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)

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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

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

Reviewer #1: No

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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

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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

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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 you for allowing me to review this revised manuscript. While much improved there are some persistent areas that require attention and revision:

1)Inclusion exclusion criteria (Line number 73 under methods)

Inclusion criteria

I.Prescriptions which had been prescribed with at least one oral dosage form of

medicine within a month from the day of data collection to children under the age of 12

years (dispensed may be a more definite word here vs prescribed?) Medication is the usual term vs medicine

II.Parents/ guardians giving the data were the ones who gave medicines to the child at

home (giving suggest change to providing)

III.Parents/ guardians should have the prescriptions with them at the time of data

collection. (recommend change "should" to must to strengthen the inclusion criteria)

Exclusion criteria

I.Prescriptions without oral dosage forms.

II.Prescriptions issued. older than one month (recommend change this sentence-doesnt make sense in current form. Suggest something similar to "Prescriptions dispensed more than 30 days prior to data collection"

Please re-review the entire manuscript carefully for correct grammar and typos

Again, suggest review by a native English speaker, perhaps not involved in the study to obtain a clear concise edited text

There are persistent grammatical and a spelling error

Please see lines 72, 194,200,206, 226,228 for revision

With respect to regression analysis, this recommendation was rejected based on that this was not in the original study question, however it may strengthen the study. If you do not wish to run the regression to provide a robust analysis of this issue, then please discuss the need to explore factors predisposing to inappropriate administration of medications by parents to children in your discussion. Thank you.

Clearly state in the Discussion section exactly how information to parents/caregivers in a busy clinic with long wait times can be provided (printed information on posters, handouts, etc)

Recommend stating clearly in a section on limitations that demographics, adherence and number of children in the household were not evaluated

When writing about the incorret use of medication dispensing devices and drugs of narrow therapeutic index, please specify the proportion of your study drugs where of this nature...for example in a regional referral center, children may receive anticoagulants, antiarryhmics, antiepileptics that require exact dosage administration

Finally, in the conclusion when stating issues, strongly recommend that some of these are stated...such as disease transmission, bioavailability, and over and underdosing. The current conclusion is rather weak.

Good luck in your final revisions!

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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

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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.

Administration of oral dosage forms of medicines to children in a resource limited setting

PONE-D-21-27919R2

Dear Dr. Nadeshkumar,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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

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: Yes

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

Reviewer #1: 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 #1: No

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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

**********

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 you again for the opportunity to review your second version of edits

Overall, the much improved and I recommend that the manuscript be accepted for publication with two minor grammatical revisions:

Line 256: re-looked -a better word may be "re-examined"

Line 257: very less - please change to "less"

(do not require the "very")

Good luck with your future work

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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

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