-->PONE-D-26-09706-->-->Drug-Induced Gastric Motility Disorders: A Disproportionality Analysis from the FAERS and CVARD Databases-->-->PLOS One

Dear Dr. Qian,

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Kind regards,

Timotius Ivan Hariyanto, 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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: 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: The article is very clear and the methodology is well described. The results are interesting, considering the widespread use of GLP-1 antagonists today and also in relation to insulin. It needs minor revisions, mainly in the writing. There are some typos that should be corrected, for example on line 98 (Mthod). It is also necessary to standardize the writing of the results, for example on lines 319 and 320.

Reviewer #2: Introduction

• Line 69 -79 – What’s the reference group (for the odd ratios) in the analysis

Methods

• Line 98 – please correct the spelling error for the heading

• Line 103 – Months or years would best describe the duration than the quarters

• Line 114 – Remove the upper case where not required

• Line 114 -115 – The sentence is not comprehensible. Try to restructure it

• Line 116-117- same as above

• Line 132 – It’s important to state the specific R package that was used in the analysis

• For logical flow, the study design subheading should come first before other sections such as definition of variables and statistical analysis

• Line 137-139 – Why have the authors only indicated the ROR and not the other other metrics as well? Further, I suggest the evaluation criteria using all the metrics be briefly described here and not just in the supplementary table. Also note that the evaluation criteria for all the three metrics (and not just the ROR) uses the lower bound limit of the 95% CI

Results

• Line 161-167 – There is no need to use upper cases for the drug names. Please revise the section. It is also important to list the drug in descending order by the signal strength

• Line 170 and other sections with similar results – Include the central value (mean or median) with the spread for the onset of action

• Line 189 – rephrase of delete the subheading

• Line 200, 201, 205 and all other sections with similar results – Include the 95%CI for the ROR

• Line 213-220- this section needs to be moved to the methods section

Limitations

• The failure to validated other signals due to use of smaller Canadian database has not been well discussed in the section. DO you suggest any another better database that can be used for further validation?

Figures

Figure 2 – Confirm if some RORs have very narrow 95% CI or they are missing on the plot?

Figure 3 – Provide a more detailed description in the legend to help interpretation of the figure. For instance, what the threshold for a signal on the log scale?

Other comments:

1. Revise to ensure logical flow of sections and information across the manuscript

2. Some subheadings are not necessary. Maintain only those that are important

3. There are too many short paragraphs. WHERE NECESSARY, combine related information into one paragraph

4. You stated that signal detection was based on the all the metrics (ROR, PRR and IC025) but in the results, the ROR is the most outstanding metric. Please make sure you highlight this in the methods and discussion sections

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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

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Drug-Induced Gastric Motility Disorders: A Disproportionality Analysis from the FAERS and CVARD Databases

PONE-D-26-09706R1

Dear Dr. Qian,

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,

Timotius Ivan Hariyanto, 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

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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

**********

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

-->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: Yes

**********

-->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: 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 #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.

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: Juliana A. C. Diel

Reviewer #2: No

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